Cell recognition and entry by rhino- and enteroviruses.
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Animals↗
Biomedical subjects
Y He
Publications and source records attributed to Y He.
Trace analysis of ten chlorinated benzenes in water by headspace solid-phase microextraction.
Headspace solid-phase microextraction (SPME), as a simple, solvent-free method, has been applied to the analysis of 10 chlorinated benzenes (CBs) present at trace levels in water samples. An SPME fibre coated with 100-microm thick poly(dimethylsiloxane) was used for extraction. The analytical data exhibited a relative standard deviation (RSD) range of 1.19% (for pentachlorobenzene) to 8.19% (for hexachlorobenzene) for the 10 CBs; the RSD of most compounds was under 6%. The sensitivity of the method was enhanced with agitation and with addition of salt to the sample solutions. With mass spectrometric detection, the limit of detection was below 0.006 microg/l for all 10 CBs after a 30-min sampling time. The linearity range was 0.02-20 microg/l for the compounds studied. Water samples collected from a reservoir, and from the tap in a laboratory were analysed using the optimised conditions.
Chlorobenzenes↗
Differential synaptic localization of the glutamate transporter EAAC1 and glutamate receptor subunit GluR2 in the rat hippocampus.
EAAC1, a neuron-specific glutamate transporter, is likely to play an important role in the regulation of glutamate levels in the synaptic cleft. Ultrastructural studies have demonstrated that the glutamate receptor subunit proteins (e.g., GluR2) are frequently preferentially located at the postsynaptic density of asymmetric synapses. While the glutamate/glutamate receptor interaction is likely to be influenced by the activity and location of the transporter molecules, the spatial localization of the transporter molecules relative to the receptor molecules is not well delineated. Thus, we analyzed the cellular, ultrastructural, and synaptic distribution of EAAC1 in the context of the distribution of the AMPA receptor subunit GluR2 in the hippocampus. While GluR2 and EAAC1 are both present in hippocampal projection neurons, their intracellular distribution patterns differ. Both GluR2 and EAAC1 are present in the dendritic membranes and cytoplasm; however EAAC1 has a distinctive punctate distribution in the dendrite compared to the more diffuse labeling reflected by GluR2. Pre-embedding ultrastructural studies also revealed cytoplasmic and membrane-associated pools of EAAC1 within dendritic shafts and spines, as well as in a subset of axonal profiles and terminals. Postembedding double label immunogold localization demonstrated a similar intraneuronal distribution, but in addition showed that membrane-associated EAAC1 is not intermingled with GluR2 within the synaptic complex, but in contrast is primarily located perisynaptically, often immediately outside the synaptic specialization. In addition, there is a significant presynaptic pool of EAAC1, whereas GluR2 is essentially absent from the pre-synaptic profile. Thus, membrane-associated EAAC1 within the synaptic region is ideally situated to restrict the site of action of glutamate with respect to ionotropic receptors to the synaptic cleft, as well as regulate glutamate levels in the perisynaptic and presynaptic domains, the ultrastructural sites that have been associated with metabotropic receptor localization.
Amino Acid Transport System X-AG↗
Pramipexole inhibits lipid peroxidation and reduces injury in the substantia nigra induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in C57BL/6 mice.
Pramipexole has been showed to protect cultured dopaminergic (DAergic) cells against free radical-induced cytotoxicity. To test if pramipexole is protective against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-mediated nigral DAergic injury in vivo and if such protection is related to inhibition of lipid peroxidation, DAergic function and lipid peroxidation were determined in MPTP-treated C57BL/6 mice. We reported that MPTP administration induced a 38.1% increase of lipid peroxidation product thiobarbituric acid reactive substance (TBARS) in nigra, a 46.7% decrease of tyrosine hydroxylase -positive nigral DAergic neurons and a 59.4% reduction of striatal DA levels. However, pramipexole treatment significantly inhibited the TBARS production by 76%, and attenuated the MPTP-induced decreases in nigral DAergic neurons and striatal DA levels by about 50%. This study suggests that pramipexole can inhibit free radical-mediated lipid peroxidation and protect MPTP-induced nigral injury.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
6-Hydroxydopamine induced apoptosis of dopaminergic cells in the rat substantia nigra.
The pathologic hallmark of Parkinson's disease is the dopaminergic cell death in the substantia nigra (SN). The cause of the cell death is, however, unknown. Even the question on whether the cells die by apoptosis or necrosis has not been answered with certainty. In 6-Hydroxydopamine induced Parkinsonian rats, the present study observed apoptotic nuclei from 1 day to 14 days after lesioning, using the TdT(terminal deoxynucleotidyl transferase)-mediated dUTP-biotin nick-end labeling method. Tyrosine hydroxylase immunohistochemistry and haematoxylin staining further revealed that these apoptotic cells are dopaminergic cells in the substantia nigra. The results suggest that dopaminergic cells in SN undergo apoptosis in the rat model of Parkinson's disease.
Animals↗
Intravenous injection of naked DNA encoding secreted flt3 ligand dramatically increases the number of dendritic cells and natural killer cells in vivo.
The trace number of dendritic cells (DCs) present in tissues has limited the study of DC biology and development of clinical applications utilizing DCs. Here we show that hydrodynamics-based gene delivery of naked DNA encoding secreted human flt3 ligand (hFLex) can dramatically increase the number of functional DCs and natural killer (NK) cells. After a single injection of the hFLex gene, hFLex levels in mouse serum reached approximately 40 microg/ml and remained above 1 microg/ml for 5-6 days. Sustained levels of serum hFLex correlated with significant increases in the size of the lymphoid organs and in the proportion of dendritic cells and NK cells in both lymph nodes and spleen. The increase in DC and NK cell numbers started from day 5, and reached peak levels between day 8 and day 12. The levels then returned to normal on day 20. These DCs and NK cells were functional as evidenced by mixed leukocyte reactions and lysis of YAC-1 cells, respectively. These results suggest that delivery of the hFLex gene provides a simple, efficient, and inexpensive way of increasing DC and NK cell populations in vivo, and may have broad applications in the further study of DC and NK cell biology and in the development of immunotherapy strategies.
Animals↗
Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro.
Trimetoquinol (1, TMQ) is a potent nonselective beta-adrenergic receptor (AR) agonist and a thromboxane A(2)/prostaglandin endoperoxide (TP) receptor antagonist, while 3',5'-diiodo-TMQ (2) exhibits beta(3)-AR selectivity. In search of selective beta(3)-AR agonists as potential drugs for the treatment of human obesity and type II diabetes mellitus, a series of 1-(3, 5-diiodo-4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ols has been prepared and evaluated for their biological activities at human beta(1)-, beta(2)-, and beta(3)-ARs expressed in Chinese hamster ovary (CHO) cells. The compounds have been synthesized by the Bischler-Napieralski cyclization of corresponding amides followed by NaBH(4) reduction, and the halogens in the aromatic ring A were introduced by direct halogenation of protected compound 11. Whereas halogen substitution in ring A reduced either potency or intrinsic activity on beta(3)-AR, the non-halogen-substituted compounds 8 and 10 were potent, selective, nearly full agonists for beta(3)-AR.
Adrenergic beta-Agonists↗
Constraining the subunit order of rod cyclic nucleotide-gated channels reveals a diagonal arrangement of like subunits.
Retinal rod cyclic nucleotide-gated channels are composed of alpha and beta subunits. We have explored possible subunit arrangements by expressing tandemly linked dimers of both subunits and examining their responses to three different modulating agents. Channels formed from either alpha-beta or beta-alpha heterodimers had functional properties similar to those formed from coexpressed alpha and beta monomers and to native channels. These results point to an alpha-beta-alpha-beta arrangement. To ensure that heterodimers had not flipped around, we coexpressed alpha-alpha dimers with an excess of either beta monomers or beta-beta dimers. Our data indicate that heteromultimers do not form efficiently in an alpha-alpha-beta-beta arrangement. Thus, we propose that native rod cyclic nucleotide-gated channels are arranged with like subunits diagonally opposed: alpha-beta-alpha-beta.
Animals↗
Interaction of the poliovirus receptor with poliovirus.
The structure of the extracellular, three-domain poliovirus receptor (CD155) complexed with poliovirus (serotype 1) has been determined to 22-A resolution by means of cryo-electron microscopy and three-dimensional image-reconstruction techniques. Density corresponding to the receptor was isolated in a difference electron density map and fitted with known structures, homologous to those of the three individual CD155 Ig-like domains. The fit was confirmed by the location of carbohydrate moieties in the CD155 glycoprotein, the conserved properties of elbow angles in the structures of cell surface molecules with Ig-like folds, and the concordance with prior results of CD155 and poliovirus mutagenesis. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. However, the orientation of the long, slender CD155 molecule relative to the poliovirus surface is quite different from the orientation of intercellular adhesion molecule-1 on rhinoviruses. In addition, the residues that provide specificity of recognition differ for the two receptors. The principal feature of receptor binding common to these two picornaviruses is the site in the canyon at which binding occurs. This site may be a trigger for initiation of the subsequent uncoating step required for viral infection.
Amino Acid Sequence↗
Interleukin-4 transgenic mice develop glomerulosclerosis independent of immunoglobulin deposition.
Mice with constitutive transgenic (tg) expression of IL-4 develop autoimmune-type disorders resembling human lupus nephritis. The kidneys show progressive glomerulosclerosis with immunoglobulin (Ig) and complement deposition. This study investigated the roles of renal IL-4 expression and glomerular Ig deposition in the pathogenesis of glomerulosclerosis in IL-4 tg mice. Treatment of these mice with IL-4 neutralizing antibody prevented renal disease. IL-4 tg mice treated with methylprednisolone (MP) showed increased mesangial collagen deposition with only trace amounts of glomerular Ig. To analyze the relevance of Ig deposition in the development of the renal lesions, IL-4 tg mice were cross-bred with mu chain-deficient mice (muMT-/-), which are unable to produce Ig. IL-4 tg/muMT-/- mice developed progressive glomerulosclerosis with mesangial accumulation of collagen types I, IV and V despite complete absence of glomerular Ig deposits. Renal IL-4 expression was observed in both anti-IL-4- and MP-treated IL-4 tg mice as well as in IL-4 tg/muMT-/- mice. No statistical difference in the number of glomerular T cells and macrophages between any of the groups was evident. Our data demonstrate that in this model glomerulosclerosis can develop independently of and prior to Ig deposition, and suggest that the initial accumulation of glomerular extracellular matrix is due to renal IL-4 expression. Our results point to a novel mechanism for the development of glomerulosclerosis which may have implications for human disease.
Animals↗
Clinical correlates of 6-hydroxydopamine injections into A11 dopaminergic neurons in rats: a possible model for restless legs syndrome.
Pursuant to the clinical suspicion that restless legs syndrome (RLS) may involve dopaminergic diencephalic spinal neurons (A11), we performed stereotaxic bilateral 6-hydroxydopamine (6-OHDA) lesions into the A11 nucleus to observe for any behavioral correlates similar to this clinical condition. Pathologic examination demonstrated a 54% reduction in A11 tyrosine hydroxylase staining cells in rats injected with 6-OHDA versus sham treatment. Multiple blindly rated 90-120-minute video epochs demonstrated an increased average number of standing episodes (14.4+/-11.7 versus 7.3+/-5.5 episodes/epoch) and increased total standing time (38.9+/-20.5 versus 25.3+/-12.2 minutes/epoch) but similar total sleep time in four lesioned rats when compared with two sham rats. Treatment of the lesioned rats with intramuscular pramipexole subsequently resulted in fewer standing episodes (4.4+/-3.3 versus 14.4+/-11.7 episodes/epoch) and less total standing time (20.9+/-12.3 versus 38.9+/-20.5 minutes/epoch) when compared with untreated lesioned rats. Despite a large number of observations, the small number of lesioned animals precluded formal statistical analysis. These behaviors are consistent, although not specific, with what would be expected in an animal model of RLS.
Adrenergic Agents↗
Comparison of physical dependence of ohmefentanyl stereoisomers in mice.
Stereo-structural difference of ohmefentanyl stereoisomers on analgesic action and receptor affinity has been studied. To assess the difference of ohmefentanyl stereoisomers in physical dependence, the potency of physical dependence was quantified by estimating the ED50 value of ohmefentanyl stereoisomers in the naloxone-precipitated jumping test in mice. Morphine was used to assess the method and as a drug of comparison. The results indicate that the degree of physical dependence of morphine can been quantified by estimating the ED50 value of morphine withdrawal jumping induced by naloxone. A significant difference was observed in withdrawal jumping ED50 values among ohmefentanyl stereoisomers. Of these isomers, F9202 and F9204 had similarly potent analgesic action, but very significant difference in naloxone precipitated withdrawal response. Dependent potency index of F9204 was 618-fold weaker than that of F9202. It is concluded that a stereo-structural difference in physical dependence is found to exist among ohmefentanyl stereoisomers. Compound F9204 displayed a strong analgesic action and weak physical dependent potency.
Analgesics↗
Angiogenic growth factor expression in placenta.
New blood vessel growth is generally a rare event in the healthy adult. However, a notable exception to this is the female reproductive tract where cyclic angiogenesis occurs. Striking new vessel growth and remodeling also occurs during placentation; thus angiogenesis is essential for reproductive success. Vascular endothelial growth factor is a potent stimulator of this process and its production and action is tightly regulated. Indeed the placenta is a rich source of a soluble variant of the flt-1 receptor which seems to protect the placenta from the effects of excess vascular endothelial growth factor. The balance between new vessel growth (in the placental villi for example) and endothelial cell loss in the spiral arteries within the decidua is a delicate one. This is influenced by the local production of promotors and inhibitors of endothelial cell activation. Perturbation of this may lead to maternal pathology during pregnancy.
Angiogenesis Inducing Agents↗
Estimation of wrist fracture load using phalangeal speed of sound: an in vitro study.
This study aimed to evaluate the ability of speed of sound (SOS) measured at the phalanges to estimate simulated wrist fracture load and stress. SOS was measured along the proximal phalanges of the second, third and fourth fingers using an ultrasound (US) system operating in axial transmission mode. The bone mineral density (BMD) of the radius and the phalanges was also measured with quantitative computed tomography (QCT) and dual x-ray absorptiometry (DXA), and the combined cortical thickness (CCT) of the phalanges was measured from hand radiographs. After the measurements were completed, the radius was excised from the cadaver, embedded in polymethylmethacrylate and tested to failure on a servohydraulic testing machine. The configuration of the radius was chosen to simulate a fall onto the hand. Linear regression analysis showed a highly significant correlation between SOS (r = 0.76-0.94, p < 0.001), CCT (r = 0.86-0.90, p < 0.001) and BMD (r = 0.92-0.96, p < 0.0001) in the three proximal phalanges measured. SOS, BMD and CCT were significant predictors of fracture load (r = 0.60-0.69, p < 0.03) and stress (r = 0.65-0.77, p < 0.02). Cortical area and bone mineral content (BMC) of the radius were consistently higher predictors of fracture load (r = 0.76-0.82, p < 0.01 for area and r = 0.78-0.88, p < 0.01 for BMC) than BMD. The correlation of BMC and area was poorer with fracture stress. In a step-wise regression analysis using both phalangeal BMD and SOS, only SOS remained a significant predictor of fracture stress. In forward stepwise regression analysis, both cortical area and SOS were entered into the regression model to estimate fracture load. Only SOS remained significant in the model for estimating fracture stress. Phalangeal BMD was only entered in the combined model with the cortical area at the 4% site (r = 0.84, p = 0.002). Phalangeal SOS is a useful parameter in the assessment of bone status of the radius.
Absorptiometry, Photon↗
atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain.
Drosophila atonal (ato) is the proneural gene of the chordotonal organs (CHOs) in the peripheral nervous system (PNS) and the larval and adult photoreceptor organs. Here, we show that ato is expressed at multiple stages during the development of a lineage of central brain neurons that innervate the optic lobes and are required for eclosion. A novel fate mapping approach shows that ato is expressed in the embryonic precursors of these neurons and that its expression is reactivated in third instar larvae (L3). In contrast to its function in the PNS, ato does not act as a proneural gene in the embryonic brain. Instead, ato performs a novel function, regulating arborization during larval and pupal development by interacting with Notch.
Animals↗
BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control.
BCL-6, a transcriptional repressor frequently translocated in lymphomas, regulates germinal center B cell differentiation and inflammation. DNA microarray screening identified genes repressed by BCL-6, including many lymphocyte activation genes, suggesting that BCL-6 modulates B cell receptor signals. BCL-6 repression of two chemokine genes, MIP-1alpha and IP-10, may also attenuate inflammatory responses. Blimp-1, another BCL-6 target, is important for plasmacytic differentiation. Since BCL-6 expression is silenced in plasma cells, repression of blimp-1 by BCL-6 may control plasmacytic differentiation. Indeed, inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1. These data suggest that malignant transformation by BCL-6 involves inhibition of differentiation and enhanced proliferation.
Animals↗
Prediction of bone strength of distal forearm using radius bone mineral density and phalangeal speed of sound.
This investigation compares quantitative ultrasound (QUS) measurement of the phalanges with peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA) measurement of the forearm, to estimate the strength of the distal radius in 13 cadaveric forearms. The cadavers were scanned at the distal radius by pQCT and DXA for bone mineral density (BMD) and at the approximate phalanges by QUS for speed of sound (SOS). The distal radii were subjected to a simulated Colles fracture produced with a materials testing machine. The load at which the distal radius was fractured was considered as a representation of bone strength. The bone strength correlated significantly with SOS at different phalanges (r = 0.63-0.72), BMD at different regions of interest by DXA (r = 0.67-0.75), and cortical BMD at different sites by pQCT (r = 0.61-0.67). Standard stepwise regression analysis showed that adding phalangeal SOS into forearm densitometric variables significantly enhanced the statistical power for prediction of the strength of the distal radius. Our results suggest that, for assessment of site-specific distal forearm strength, QUS measurement of the phalanges is comparable to forearm densitometry. Phalangeal QUS may add clinical value if distal forearm strength has a high priority.
Aged↗
Field performance of transgenic elite commercial hybrid rice expressing bacillus thuringiensis delta-endotoxin.
Here we describe development of transgenic elite rice lines expressing a Bt fusion gene derived from cryIA(b) and cryIA(c) under the control of rice actinI promoter. The lines used in the study were indica CMS restorer line of Minghui 63 and its derived hybrid rice Shanyou 63. The level of Bt fusion protein CryIA(b)/CryIA(c) detected in Minghui 63 (T51-1) plants was 20 ng/mg soluble protein. The Bt Shanyou 63 was field-tested in natural and repeated heavy manual infestation of two lepidopteran insects, leaffolder and yellow stem borer. The transgenic hybrid plants showed high protection against both insect pests without reduced yield.
Actins↗