Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 19 recordsLinked to original sources

PubMed2006

Role of acetylcholine transmission in nucleus accumbens and ventral tegmental area in heroin-seeking induced by conditioned cues.

The involvement of cholinergic transmission in heroin self-administration and the reinstatement of heroin-seeking was examined in rats trained to nose-poke for i.v. heroin. Systemic treatment with physostigmine, an inhibitor of acetylcholinesterase, modestly reduced the acquisition and rate of heroin self-administration, and this suppression of heroin intake was reversed by pretreatment with scopolamine but not by mecamylamine. Following 10-14 days of self-administration, rats were left in the home environment for 14 days. Subsequently, rats were evaluated for extinction of nose-pokes during the first hour after being returned to the self-administration apparatus. One hour later a conditioned stimulus (house light, light in the nose-poke hole, sound of the infusion pump) was presented to initiate cue-induced reinstatement. Physostigmine produced a dose-dependent inhibition of cue-induced reinstatement, but only the dose of 0.5 mg/kg significantly decreased nose-poke responding in the extinction test. Chronic treatment with physostigmine (0.1 mg/kg) did not impair performance during acquisition of heroin self-administration. However, during a subsequent reinstatement test conducted in the absence of physostigmine pretreatment, heroin seeking was significantly below that of rats chronically pretreated with saline. To evaluate brain regions mediating the effects of systemic drug treatment on reinstatement, physostigmine was microinjected into the nucleus accumbens (NAc) or ventral tegmental area (VTA). Microinjection of physostigmine into the NAc prior to presenting conditioned cues inhibited the reinstatement of heroin-seeking, without affecting extinction responding. In contrast, microinjection of physostigmine into the VTA augmented the reinstatement induced by conditioned cues and extinction responding. Inactivation of either NAc or VTA by microinjecting tetrodotoxin blocked both extinction responding and cue-induced reinstatement. These data demonstrate that cholinergic transmission influences heroin self-administration and reinstatement. Moreover, cue-induced reinstatement was inhibited by physostigmine in the NAc and potentiated by cholinergic stimulation in the VTA.

Acetylcholine↗

PubMed2006

PATRIC: the VBI PathoSystems Resource Integration Center.

The PathoSystems Resource Integration Center (PATRIC) is one of eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infection Diseases (NIAID) to create a data and analysis resource for selected NIAID priority pathogens, specifically proteobacteria of the genera Brucella, Rickettsia and Coxiella, and corona-, calici- and lyssaviruses and viruses associated with hepatitis A and E. The goal of the project is to provide a comprehensive bioinformatics resource for these pathogens, including consistently annotated genome, proteome and metabolic pathway data to facilitate research into counter-measures, including drugs, vaccines and diagnostics. The project's curation strategy has three prongs: 'breadth first' beginning with whole-genome and proteome curation using standardized protocols, a 'targeted' approach addressing the specific needs of researchers and an integrative strategy to leverage high-throughput experimental data (e.g. microarrays, proteomics) and literature. The PATRIC infrastructure consists of a relational database, analytical pipelines and a website which supports browsing, querying, data visualization and the ability to download raw and curated data in standard formats. At present, the site warehouses complete sequences for 17 bacterial and 332 viral genomes. The PATRIC website (https://patric.vbi.vt.edu) will continually grow with the addition of data, analysis and functionality over the course of the project.

Bioterrorism↗

PubMed2006

A crossed beams study of the reaction of carbon atoms, C(3Pj), with vinyl cyanide, C2H3CN(X 1A')--investigating the formation of cyano propargyl radicals.

The chemical dynamics of the reaction of ground state carbon atoms, C(3Pj), with vinyl cyanide, C2H3CN(X 1A'), were examined under single collision conditions at collision energies of 29.9 and 43.9 kJ mol(-1) using the crossed molecular beams approach. The experimental studies were combined with electronic structure calculations on the triplet C4H3N potential energy surface (H. F. Su, R. I. Kaiser, A. H. H. Chang, J. Chem. Phys., 2005, 122, 074320). Our investigations suggest that the reaction follows indirect scattering dynamics via addition of the carbon atom to the carbon-carbon double bond of the vinyl cyanide molecule yielding a cyano cyclopropylidene collision complex. The latter undergoes ring opening to form cis/trans triplet cyano allene which fragments predominantly to the 1-cyano propargyl radical via tight exit transition states; the 3-cyano propargyl isomer was inferred to be formed at least a factor of two less; also, no molecular hydrogen elimination channel was observed experimentally. These results are in agreement with the computational studies predicting solely the existence of a carbon versus hydrogen atom exchange pathway and the dominance of the 1-cyano propargyl radical product. The discovery of the cyano propargyl radical in the reaction of atomic carbon with vinyl cyanide under single collision conditions implies that this molecule can be an important reaction intermediate in combustion flames and also in extraterrestrial environments (cold molecular clouds, circumstellar envelopes of carbon stars) which could lead to the formation of cyano benzene (C6H5CN) upon reaction with a propargyl radical.

Journal Article↗

PubMed2006

Identification of a novel splice variant of AML1b in ovarian cancer patients conferring loss of wild-type tumor suppressive functions.

Acute myeloid leukemia (AML) 1 is often disrupted by chromosomal translocations generating oncogenic fusions in human leukemias. However, its role in epithelial cancers has not been extensively investigated. Herein, we show a marked accumulation of AML1 transcripts including a high frequency of a novel alternatively spliced AML1b transcript lacking exon 6 (AML1b(Del179-242)) in ovarian cancer patients. The increases in RNA transcripts for total wild-type AML1 and AML1b(Del179-242) are associated with poor patient outcomes. We have shown that although both wild-type AML1b and AML1b(Del179-242) are localized to nuclear speckles, AML1b(Del179-242) was observed to have dramatically reduced transactivation potential with the plasminogen activator inhibitor-1 promoters and behaved as a weak dominant negative of wild-type AML1b. Wild-type AML1b was found to inhibit the growth of immortalized ovarian epithelial cells (T29) decreasing colony-forming ability. Moreover, we have identified a novel function of AML1b where it inhibits ovarian cell migration. In contrast, AML1b(Del179-242) has lost the ability to inhibit both ovarian cell proliferation and migration indicating that the functional effects observed with wild-type AML1b are dependent on amino acids 179-242. Collectively, these studies suggest that deregulated alternative splicing of AML1b transcripts may potentially contribute to the pathophysiology of ovarian cancers.

Alternative Splicing↗

PubMed2006

Effect of ammonium and nitrate nutrition on some physiological processes in higher plants - growth, photosynthesis, photorespiration, and water relations.

Ammonium and nitrate as different forms of nitrogen nutrients impact differently on some physiological and biochemical processes in higher plants. Compared to nitrate, ammonium results in small root and small leaf area, which may contribute to a low carbon gain, and an inhibition on growth. On the other hand, due to (photo)energy saving, a higher CO (2) assimilation rate per leaf area was observed frequently in plants supplied with ammonium than in those supplied with nitrate. These results were dependent not only on higher Rubisco content and/or activity, but also on RuBP regeneration rate. The difference in morphology such as chloroplast volume and specific leaf weight might be the reason why the CO (2) concentration in the carboxylation site and hence the photorespiration rate differs in plants supplied with the two nitrogen forms. The effect of nitrogen form on water uptake and transportation in plants is dependent both on leaf area or shoot parameter, and on the root activity (i.e., root hydraulic conductivity, aquaporin activity).

Biological Transport↗

PubMed2006

Systematic method to new phases of polymeric nitrogen under high pressure.

A systematic method to unravel a large class of single-bonded (SB) polymeric phases of nitrogen under high pressure is presented. The approach is based on the combinatorial generation of different Peierls-like distortions of a given reference structure that maintain the threefold connectivity of SB nitrogen, followed by first-principles calculations. Using an eight atom simple cubic reference structure, the approach not only recovers all four SB nitrogen phases reported to date, but eight new metastable structures (confirmed by phonon density of states calculations) are found. Basic properties of the structures are computed and the trends analyzed. Extensions to the method are straightforward and should lead to the discovery of more phases of polynitrogen.

Journal Article↗

PubMed2006

Food remains in Confuciusornis sanctus suggest a fish diet.

Despite hundreds of excellent fossils of Confuciusornis, the most abundant group of birds in the Early Cretaceous, 'Jehol Biota' in China, there is yet no indication of the food choice of these birds. Here, we describe fish remains preserved in the alimentary system of a specimen of Confuciusornis sanctus from the Jiufotang Formation. This find is about five million years younger than all previously published confuciusornithid birds from the Yixian Formation. Although it is unknown how common fish was in the diet of Confuciusornis, the find does not support previous hypotheses that it fed on plants or grain.

Animal Feed↗

PubMed2006

Identification of mutations that disrupt phosphorylation-dependent nuclear export of cyclin D1.

Although cyclin D1 is overexpressed in a significant number of human cancers, overexpression alone is insufficient to promote tumorigenesis. In vitro studies have revealed that inhibition of cyclin D1 nuclear export unmasks its neoplastic potential. Cyclin D1 nuclear export depends upon phosphorylation of a C-terminal residue, threonine 286, (Thr-286) which in turn promotes association with the nuclear exportin, CRM1. Mutation of Thr-286 to a non-phosphorylatable residue results in a constitutively nuclear cyclin D1 protein with significantly increased oncogenic potential. To determine whether cyclin D1 is subject to mutations that inhibit its nuclear export in human cancer, we have sequenced exon 5 of cyclin D1 in primary esophageal carcinoma samples and in cell lines derived from esophageal cancer. Our work reveals that cyclin D1 is subject to mutations in primary human cancer. The mutations identified specifically disrupt phosphorylation of cyclin D1 at Thr-286, thereby enforcing nuclear accumulation of cyclin D1. Through characterization of these mutants, we also define an acidic residue within the C-terminus of cyclin D1 that is necessary for recognition and phosphorylation of cyclin D1 by glycogen synthase kinase-3 beta. Finally, through construction of compound mutants, we demonstrate that cell transformation by the cancer-derived cyclin D1 alleles correlates with their ability to associate with and activate CDK4. Our data reveal that cyclin D1 is subject to mutations in primary human cancer that specifically disrupt phosphorylation-dependent nuclear export of cyclin D1 and suggest that such mutations contribute to the genesis and progression of neoplastic growth.

Alleles↗

PubMed2006

Laser-induced chorioretinal venous anastomosis using combined lasers with different wavelengths.

AIM: To evaluate the effectiveness of combined lasers with different wavelengths in creating chorioretinal venous anastomosis (CRVA) in nonischaemic central retinal vein occlusion (CRVO). METHODS: In this retrospective, noncomparative, consecutive case series, records of all patients with a diagnosis of nonischaemic CRVO who underwent combined laser treatment to induce CRVA and who were followed-up for 6 months or longer were reviewed. RESULTS: Records of 85 patients (85 eyes) were analysed. These patients were divided into two groups. In group 1 (24 cases, 24 eyes), combined lasers with two different wavelengths (argon blue-green laser combined with Nd-YAG laser were used. In group 2 (61 cases, 61 eyes), combined lasers with three different wavelengths (argon blue-green laser combined with krypton red laser and Nd-YAG laser) were used. Functional anastomosis formed in 13 out of 24 eyes (54%) in group 1 and 47 out of 61 eyes (77%) in group 2. In patients with successful anastomosis, visual acuity improved for two or more lines in 49 out of 60 eyes (82%), with the remaining eyes undergoing no change. There were no serious complications. CONCLUSION: The use of three laser wavelengths results in the creation of laser anastomosis and the success rate may be higher than when using two wavelengths alone.

Adolescent↗

PubMed2006

Inducible nitric oxide synthase activity is essential for inhibition of prostatic tumor growth by interferon-beta gene therapy.

We have previously reported that adenoviral vector-mediated interferon (IFN)-beta gene therapy inhibits orthotopic growth of human prostate cancer cells in nude mice. The purpose of this study was to determine efficacy and mechanisms of this therapy in immune-competent mice. TRAMP-C2Re3 mouse prostate cancer cells infected with 100 multiplicity of infection (MOI) of adenoviral vector encoding for mouse IFN-beta (AdmIFN-beta), but not AdE/1 (a control adenoviral vector), produced approximately 60 ng/10(5) cells/24 h of IFN-beta. The tumorigenicity of AdmIFN-beta-transduced cells was dramatically reduced in the prostates of C57BL/6 mice. A single intratumoral injection of 2 x 10(9) PFU (plaque-forming unit) of AdmIFN-beta inhibited tumor growth by 70% and prolonged survival of tumor-bearing mice. Intriguingly, this AdmIFN-beta therapy did not alter the growth of tumors in inducible nitric oxide synthase (iNOS)-null C57BL/6 mice. Immunohistochemical analysis revealed that treatment of tumors with AdmIFN-beta in wild-type C57BL/6 mice led to increased iNOS expression, decreased microvessel density, decreased cell proliferation, and increased apoptosis. Furthermore, quantitative reverse-transcriptional PCR analysis showed that AdmIFN-beta therapy, in C57BL/6 but not the iNOS-null counterparts, reduced levels of the mRNAs for angiopoietin, basic fibroblast growth factor, matrix metalloproteinase-9, transforming growth factor-beta1, vascular endothelial growth factor (VEGF)-A, and VEGF-B, as well as the antiapoptotic molecule endothelin-1. These data indicated that IFN-beta gene therapy could be effective alternative for the treatment of locally advanced prostate cancer and suggest an obligatory role of NO in IFN-beta antitumoral effects in vivo.

Adenoviridae↗

PubMed2006

Activation of FGFR1beta signaling pathway promotes survival, migration and resistance to chemotherapy in acute myeloid leukemia cells.

Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and have been implicated in the tumorigenesis of solid tumors. Recent evidence suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise mechanism and specific FGF receptors that support leukemic cell growth are not known. We show that FGF-2, through activation of FGFR1beta signaling, promotes survival, proliferation and migration of AML cells. Stimulation of FGFR1beta results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1beta signaling and inhibits tumor growth in mice xenotransplanted with human AML. These data suggest that activation of FGF-2/FGFR1beta supports progression and chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of therapeutic benefit in subsets of AML.

Acute Disease↗

PubMed2006

Immediate mandibular reconstruction with microsurgical fibula flap transfer following wide resection for ameloblastoma.

Ameloblastoma, the most common odontogenic tumor, is a slow growing, localized tumor of the facial skeleton. Eighty percent of the tumors affect the mandible. Treatment by wide excision is curative in 95% of cases. Reconstruction by bone grafting has a 20% to 30% nonunion rate. We have treated three large ameloblastomae (>6 cm) with fibula flaps, following resection. All patients have healed. With follow-up times of 2 to 3 years, there has been no evidence of recurrence and no difficulties with postoperative evaluation for recurrent disease. We conclude that the fibula flap is a reliable reconstructive operation following resection of large ameloblastomae.

Adult↗

PubMed2006

Dynamic mechanics in the pig mandibular symphysis.

During mastication, various biomechanical events occur at the mammalian jaw symphysis. Previously, these events have been studied in the static environment, or by direct recording of surface bone strains. Thus far, however, it has not been possible to demonstrate directly the forces and torques passing through the symphysis in association with dynamically changing muscle tensions. Therefore, we modified a previously published dynamic pig jaw model to predict the forces and torques at the symphysis, and related these to simulated masticatory muscle tensions, and bite, joint and food bolus forces. An artificial rigid joint was modelled at the symphysis, allowing measurements of the tri-axial forces and torques passing through it. The model successfully confirmed three previously postulated loading patterns at the symphysis. Dorsoventral shear occurred when the lower teeth hit the artificial food bolus. It was associated with balancing-side jaw adductor forces, and reaction forces from the working-side bite point. Medial transverse bending occurred during jaw opening, and was associated with bilateral tensions in the lateral pterygoid. Lateral transverse bending (wishboning) occurred at the late stage of the power stroke, and was associated with the actions of the deep and superficial masseters. The largest predicted force was dorsoventral shear force, and the largest torque was a 'wishboning' torque about the superoinferior axis. We suggest that dynamic modelling offers a new and powerful method for studying jaw biomechanics, especially when the parameters involved are difficult or impossible to measure in vivo.

Animals↗

PubMed2006

Irreversible aggregation of protein synthesis machinery after focal brain ischemia.

Focal brain ischemia leads to a slow type of neuronal death in the penumbra that starts several hours after ischemia and continues to mature for days. During this maturation period, blood flow, cellular ATP and ionic homeostasis are gradually recovered in the penumbral region. In striking contrast, protein synthesis is irreversibly inhibited. This study used a rat focal brain ischemia model to investigate whether or not irreversible translational inhibition is due to abnormal aggregation of translational complex components, i.e. the ribosomes and their associated nascent polypeptides, protein synthesis initiation factors and co-translational chaperones. Under electron microscopy, most rosette-shaped polyribosomes were relatively evenly distributed in the cytoplasm of sham-operated control neurons, but clumped into large abnormal aggregates in penumbral neurons subjected to 2 h of focal ischemia followed by 4 h of reperfusion. The abnormal ribosomal protein aggregation lasted until the onset of delayed neuronal death at 24-48 h of reperfusion after ischemia. Biochemical study further suggested that translational complex components, including small ribosomal subunit protein 6 (S6), large subunit protein 28 (L28), eukaryotic initiation factors 2alpha, 4E and 3eta, and co-translational chaperone heat-shock cognate protein 70 (HSC70) and co-chaperone Hdj1, were all irreversibly clumped into large abnormal protein aggregates after ischemia. Translational complex components were also highly ubiquitinated. This study clearly demonstrates that focal ischemia leads to irreversible aggregation of protein synthesis machinery that contributes to neuronal death after focal brain ischemia.

Analysis of Variance↗

PubMed2006

A frequent partial AZFc deletion does not render an increased risk of spermatogenic impairment in East Asians.

The gene families in the AZFc region of the Y chromosome have been shown to be functionally important in human spermatogenesis. The gr/gr deletion, a partial AZFc deletion that reduces the copy numbers of all the AZFc gene families, was identified as a significant risk factor for spermatogenic impairment in Dutch, Spanish and Italians. However, the presence of this deletion in healthy French and Germans questioned its importance in male infertility. In this study, we have shown that the gr/gr deletion does not render an increased risk in Han Chinese. In fact, the gr/gr deletion is frequent (about 8%) in our survey of 886 East Asians from 8 ethnic groups. Furthermore, the DAZ1/DAZ2 deletion has been detected as the primary subtype of the gr/gr deletion in East Asians, though this doublet has been considered as crucial for normal spermatogenesis in Europeans. The different spermatogenic effects of various types of the partial AZFc deletion suggest that the functional difference between AZFc gene copies is a likely cause of inconsistent associations of the gr/gr deletion with spermatogenic impairment across populations.

Base Sequence↗

PubMed2006

Sequence variations in the MBL gene and their relationship to pulmonary tuberculosis in the Chinese Han population.

SETTING: The mannan binding lectin (MBL) gene is thought to play a role in human innate immune response to tuberculosis (TB) infection. OBJECTIVE: To investigate the possible association between MBL sequence variants and TB infection in the Chinese Han population. DESIGN: A total of 152 male pulmonary tuberculosis (PTB) patients and 293 healthy male subjects were recruited. Six MBL single nucleotide polymorphisms (SNPs) (A/B, A/C, A/D, H/L, Y/X and P/Q) were genotyped and haplotyped using the combined analysis of polymerase chain reaction using sequence-specific primers (PCR-SSP) and the PCR-sequence specific oligonucleotide probe (PCR-SSOP) assay. The genotype and haplotype frequencies were compared between TB cases and controls using an unconditional logistic regression model. RESULTS: Neither the genotypes nor the haplotypes of the five loci were significantly associated with the disease when considered individually. After the haplotypes were regrouped, however, the XB haplotype group coding for diminished MBL levels was present at a significantly higher frequency in the patients compared with the YA group (OR 1.57, 95% CI 1.02-2.41, P < 0.05). CONCLUSION: No convincing evidence of association between MBL sequence variants and PTB was observed individually, although the low-producing XB haplotype group may serve as a minor risk factor for PTB infection in the male Chinese Han population.

Adolescent↗

PubMed2005

Characterization of epitopes for neutralizing monoclonal antibodies to classical swine fever virus E2 and Erns using phage-displayed random peptide library.

Infection of cells with classical swine fever virus (CSFV) is mediated by the interaction of envelope glycoproteins E2 and Erns with receptor molecules on the cell surface. These proteins are also the major antigens for eliciting neutralizing antibodies and conferring protective immunity. Here we report the identification of multiple neutralizing epitopes on these proteins by screening a phage-displayed random peptide library with CSFV-specific neutralizing monoclonal antibodies. Two different E2-specific neutralizing mAbs (a18 and 24/10) were found to bind to a common motif SPTxL, which is similar to the sequence SPTTL of the E2 protein (aa 289-293), indicating that this is likely to be an immunodominant epitope. Similarly, an immunodominant epitope corresponding to the sequence DKN of Erns (aa 117-119) was identified for two independent Erns-specific neutralizing antibodies, b4-22 and 24/16, respectively. Another binding motif, CxNNxTC, was identified for mAb 24/16, but not for b4-22. Sequencing analysis of the genes coding for the light chain of these mAbs was conducted to ensure that all mAbs were derived from different hybridomas, rather than from different subclones of a common parent line. Inhibition studies using immunofluorescent antibody assay and virus neutralization test demonstrated that the mimotope peptides truly mimicked the antibody binding determinants on the viral proteins. The detailed mapping data for these neutralizing epitopes will be useful for development of improved diagnostic tests and perhaps a peptide-based vaccine for this important swine disease.

Amino Acid Motifs↗

PubMed2005

Application of direct covalent molecular assembly in the fabrication of polyimide ultrathin films.

Ultrathin films were fabricated using synthesized hydroxyl polyimide (HPI) in a layer-by-layer fashion on amine-terminated substrates of silicon, quartz, and gold. The interlayer linkages were established by using terephthaloyl chloride as a bridging agent to form ester groups between HPI layers. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-vis absorption spectroscopy, atomic force microscopy, ellipsometry, and electrochemical impedance spectroscopy were employed to study the interfacial chemistry, stepwise growth, morphology, thickness, optical property, and insulation behavior of the assembled film. The films show excellent stability and strength, which can be attributed to the covalent interlayer linkage.

Journal Article↗