The corral hypothesis: a novel regulatory mode for retinoblastoma protein function.
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Animals↗
Biomedical subjects
Y Xu
Publications and source records attributed to Y Xu.
Modified formula of nonlocal electron transport in a laser-produced plasma.
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Journal Article↗
Hidden Markov model approach to skill learning and its application to telerobotics.
In this paper, we discuss the problem of how human skill can be represented as a parametric model using a hidden Markov model (HMM), and how an HMM-based skill model can be used to learn human skill. HMM is feasible to characterize a doubly stochastic process--measurable action and immeasurable mental states--that is involved in the skill learning. We formulated the learning problem as a multidimensional HMM and developed a testbed for a variety of skill learning applications. Based on "the most likely performance" criterion, the best action sequence can be selected from all previously measured action data by modeling the skill as an HMM. The proposed method has been implemented in the teleoperation control of space station robot system, and some important implementation issues have been discussed. The method allows a robot to learn human skill in certain tasks and to improve motion performance.
Algorithms↗
Characterization of expression and modulation of cell adhesion molecules on an immortalized human dermal microvascular endothelial cell line (HMEC-1).
We have recently reported the creation of the first immortalized cell line derived from human dermal microvascular endothelial cells (HMEC-1). In preliminary studies this line was found to closely resemble microvascular endothelial cells in regard to many phenotypic characteristics. Because two key functional features of endothelial cells are their ability to bind to peripheral blood leukocytes and extracellular matrix proteins via cell adhesion molecules, we have now characterized HMEC-1 in terms of expression and regulation of cell adhesion molecules of the integrin, immunoglobulin gene superfamily, and selectin families. HMEC-1 can either constitutively express or can be induced to express key integrins, including alpha-1, -2, -3, -4, -5, -6, and -V, as well as beta-1, -3, -4, and -5. They also express or are capable of expressing immunoglobulin gene superfamily molecules, such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and a member of the selectin family, E-selectin. A number of important cell adhesion molecules that are either constitutively expressed or that must be induced are regulated in a time- and dose-dependent fashion by selected cytokines. Experiments comparing the phenotypic characteristics of HMEC-1 with human dermal microvascular endothelial cells or human umbilical vein endothelial cells reveal HMEC-1 to have features of both small- and large-vessel endothelial cells.
Capillaries↗
The role of adhesion molecules in cutaneous inflammation.
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Cell Adhesion Molecules↗
Production and perception of coarticulated tones.
In the present study, the distinctive tones of Mandarin were found to coarticulate with adjacent tones in running speech. However, the amount of deviation of a tone from its canonical form due to coarticulation varied depending on the nature of the tonal context. In a context where adjacent tonal values agree (a "compatible" context), the deviation was relatively small. In a context where adjacent tonal values disagree (a "conflicting" context), the deviation was much greater, sometimes even to the extent of changing the direction of a dynamic tone. To examine the perception of coarticulated tones, naturally produced words and phrases were used as stimuli for tone identification. However, their semantic information was removed through waveform editing while all the tonal information contained in the signal remained intact. Identification of tones in the compatible context was highly accurate with or without the original tonal context. Tonal identification for the conflicting context remained accurate only when the tones were presented with the original tonal context. Without the original context, i.e., in isolation, correct tone identification dropped below chance. When the original tonal context was altered, listeners compensated for the altered context as if it had been there originally. It thus seems that, in tone perception, listeners compensate for variations due to coarticulation. Nevertheless, even with the presence of the original context, perceptual identification was better for the compatible context than for the conflicting context, indicating that variation due to coarticulation is not always completely compensated for by listeners.
Adult↗
Mutations in ftsZ that confer resistance to SulA affect the interaction of FtsZ with GTP.
Mutations in the essential cell division gene ftsZ confer resistance to SulA, a cell division inhibitor that is induced as part of the SOS response. In this study we have purified and characterized the gene products of six of these mutant ftsZ alleles, ftsZ1, ftsZ2, ftsZ3, ftsZ9, ftsZ100, and ftsZ114, and compared their properties to those of the wild-type gene product. The binding of GTP was differentially affected by these mutations. FtsZ3 exhibited no detectable GTP binding, and FtsZ9 and FtsZ100 exhibited markedly reduced GTP binding. In contrast, FtsZ1 and FtsZ2 bound GTP almost as well as the wild type, and FtsZ114 displayed increased GTP binding. Furthermore, we observed that all mutant FtsZ proteins exhibited markedly reduced intrinsic GTPase activity. It is likely that mutations in ftsZ that confer sulA resistance alter the conformation of the protein such that it assumes the active form.
Alleles↗
Induction of MnSOD gene expression in a hepatic model of TNF-alpha toxicity does not result in increased protein.
The model of toxic liver injury was used to examine the role of manganese superoxide dismutase (MnSOD) expression in cellular resistance to tumor necrosis factor (TNF)-alpha toxicity. The effects of the hepatotoxin D-galactosamine (GalN) and lipopolysaccharide (LPS) on hepatic and splenic TNF-alpha and MnSOD expression were studied. Treatment with GalN and LPS alone or in combination led to equivalent increases in hepatic and splenic TNF-alpha gene expression. Hepatic MnSOD mRNA levels were not affected by GalN or GalN with LPS but were increased 13-fold by LPS alone. Splenic MnSOD mRNA levels were increased twofold by GalN and 12-fold by either LPS alone or GalN plus LPS. The determination of MnSOD protein content, however, revealed no changes in hepatic or splenic steady-state levels of the protein with any of the treatments, despite the marked increases in MnSOD gene expression. Hepatic MnSOD enzyme activity was also unchanged by LPS or GalN plus LPS administration. Biosynthesis of MnSOD protein in rat hepatocytes isolated from an in vivo LPS-treated rat was unchanged compared with control. MnSOD mRNA levels were increased when GalN treatment was combined with uridine rescue, but again no change in protein was seen. The lack of any increase in MnSOD protein after GalN or LPS administration indicates that MnSOD upregulation is not involved in cellular resistance against TNF-alpha cytotoxicity in the liver in vivo.
Animals↗
Spinal cord infarcts during long-term inhibition of nitric oxide synthase in rats.
BACKGROUND AND PURPOSE: Chronic hypertension is a major predisposing factor for stroke in humans. It has recently been shown that long-term inhibition of nitric oxide synthase activity causes a gradual time-dependent increase in arterial blood pressure in rats. We used this new animal model of chronic hypertension to study the occurrence and spatial features of infarcts in the central nervous system. METHODS: Rats were treated with a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, dissolved in the drinking water at 50 mg/kg per day for 11 weeks. The brains and spinal cords of hypertensive rats with and without motion disturbances were processed for standard microscopic examination. RESULTS: Seventy-nine percent of the hypertensive rats showed motion dysfunctions, especially front leg paralysis, and/or died suddenly when their systolic blood pressure reached approximately 215 mm Hg after approximately 7 weeks of treatment. All of the hypertensive rats with stroke had spinal cord infarcts (90% at the cervical or cervicothoracic level) either alone or combined with brain lesions (30%). These structural alterations ranged from focal areas of pale, spongy tissue to large necrotic sites with vascular alterations, including thickened or fibrinoid degenerated vessel wall, macrophage invasion, and reactive astrocytes. CONCLUSIONS: Infarcts occurred in the central nervous system with a high incidence in the spinal cord of hypertensive rats in which nitric oxide synthase was chronically blocked. This location of the hypertensive neuropathologic sequelae contrasts with the model of stroke-prone spontaneously hypertensive rats. The results suggest that nitric oxide is a key factor in spinal cord arteriolar vasomotion and structure in rats.
Amino Acid Oxidoreductases↗
Immunocytochemical localization of endogenous anti-thrombin III in the vasculature of rat tissues reveals locations of anticoagulantly active heparan sulfate proteoglycans.
We localized endogenous anti-thrombin III (ATIII) by light and electron microscopic immunocytochemical staining in cryostat and ultra-thin frozen sections of 10 different rat tissues, using rabbit alpha-human ATIII antibody that was shown to crossreact strongly with rat ATIII. EM immunocytochemical methods revealed discrete deposits of endogenous ATIII (absent after heparinase treatment), and thus by inference anticoagulantly active heparan sulfate proteoglycans (HSPGs) at a resolution of 10-20 nm, or an order of magnitude better than autoradiography or LM. ATIII was found in variable amounts almost entirely in the subendothelial space of blood vessels in various rat tissues. In kidney, ATIII was found immediately beneath the endothelium, in concentrated clusters associated with the vascular basement membrane. Equally important is the observed variation in expression of ATIII in the various tissues studied (i.e., kidney > liver, aorta, lung, spleen, adrenal > intestine, muscle, brain). On the basis of these observations, we confirm a model in which vascular abluminal and, perhaps to a much smaller extent, luminal anticoagulantly active HSPGs regulate coagulation mechanism activity, either by serving as a reserve of anticoagulant or by modulating the ambient function of the coagulation cascade.
Animals↗
Pituitary and hypothalamic somatostatin receptor subtype messenger ribonucleic acid expression in the food-deprived and diabetic rat.
Prolonged food deprivation (FD) and streptozocin-induced diabetes (STZ diabetes) in the rat result in abolition of GH secretory episodes. We have previously shown that hypothalamic prepro-GRF messenger RNA (mRNA) expression is markedly reduced in the hypothalamus of FD and STZ diabetic rats, with no change in prepro-somatostatin (SRIF) mRNA and suggested that reduced GRF and increased SRIF tone explained the loss of GH secretion in FD and STZ diabetes. Altered SRIF peptide expression has been implicated in many physiological and pathological states; however, information on the regulation of SRIF receptor (SSTR) expression is lacking. Therefore, we examined the expression of mRNA for the five recently cloned SSTR subtypes in the pituitary and hypothalamus of FD and STZ diabetic rats. In addition, we measured SRIF binding to pituitary membranes of FD rats. SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 80% in the pituitary of FD rats vs. fed controls, whereas pituitary levels of SSTR4 and SSTR5 mRNA were unaffected. The pituitary plasma membrane SSTR concentration was reduced over 50% in FD vs. fed animals. However, hypothalamic levels of the five isoforms were unchanged. In STZ diabetes, pituitary SSTR1, SSTR2, and SSTR3 mRNA expression was reduced 50-80%, with levels of SSTR1 partially restored by insulin, whereas SSTR4 mRNA was unchanged. In contrast to the effect of FD, SSTR5 mRNA levels were reduced 70% in the pituitary and 30% in the hypothalamus of STZ diabetic rats, with complete restoration by insulin. Thus, SSTR subtype mRNA expression is differentially regulated in two models of GH deficiency in the rat, FD and STZ diabetes. As chronic exposure to SRIF results in desensitization of transfected SSTR2 and SSTR3, and SSTR binding is decreased in FD and STZ diabetic rats, the possibility exists that the pituitary changes result from continued exposure to SRIF. In the hypothalamus, however, regulation appears more complex. These data support a role of increased SRIF with decreased GRF in mediating the loss of GH secretion in FD and diabetes.
Animals↗
The validity of drug use reports from juvenile arrestees.
Using urine test results as a gold standard, this report evaluates the validity of illicit drug use reports for five illicit substances provided in a multisite, national interview study of juvenile arrestees. Willingness to report substance use varied according to the type of substance, the time frame for substance use reports, and the characteristics of the juveniles asked to provide the reports. Youth were particularly reluctant to disclose recent use of cocaine and heroin. Race/ethnicity and willingness to disclose other substance use were the most important predictors of cocaine use disclosure among those testing positive for this drug. Race/ethnicity differences in validity were evaluated in the context of other recent epidemiological findings from surveys of drug use in the United States. Implications for the measurement of drug use in criminal justice samples are discussed.
Adolescent↗
A comprehensive discussion of the birth gender ratio in China.
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Asia↗
An improved system for exon recognition and gene modeling in human DNA sequences.
A new version of the GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992; Uberbacher et al., 1993), called GRAIL II, has recently been developed (Xu et al., 1994). GRAIL II is a hybrid AI system that supports a number of DNA sequence analysis tools including protein-coding region recognition, PolyA site and transcription promoter recognition, gene model construction, translation to protein, and DNA/protein database searching capabilities. This paper presents the core of GRAIL II, the coding exon recognition and gene model construction algorithms. The exon recognition algorithm recognizes coding exons by combining coding feature analysis and edge signal (acceptor/donor/translation-start sites) detection. Unlike the original GRAIL system (Uberbacher and Mural, 1991; Mural et al., 1992), this algorithm uses variable-length windows tailored to each potential exon candidate, making its performance almost exon length-independent. In this algorithm, the recognition process is divided into four steps. Initially a large number of possible coding exon candidates are generated. Then a rule-based prescreening algorithm eliminates the majority of the improbable candidates. As the kernel of the recognition algorithm, three neural networks are trained to evaluate the remaining candidates. The outputs of the neural networks are then divided into clusters of candidates, corresponding to presumed exons. The algorithm makes its final prediction by picking the best canadidate from each cluster. The gene construction algorithm (Xu, Mural and Uberbacher, 1994) uses a dynamic programming approach to build gene models by using as input the clusters predicted by the exon recognition algorithm. Extensive testing has been done on these two algorithms.(ABSTRACT TRUNCATED AT 250 WORDS)
Algorithms↗
NAD(P)H:quinone oxidoreductase1 (DT-diaphorase): expression, regulation, and role in cancer.
NAD(P)H:quinone oxidoreductase1 (DT-diaphorase or NQO1) is a flavoprotein that promotes obligatory two-electron reduction of quinones, preventing their participation in redox cycling, oxidative stress, and neoplasia. NQO1 is ubiquitously expressed. However, a large amount of variation in NQO1 gene expression was noticed among various human tissues. NQO1 gene is upregulated in livers of hepatocarcinoma patients, and its expression is induced in response to a variety of compounds, including planar aromatic hydrocarbons, phenolic antioxidants/chemoprotectors, tumor promoters, and hydrogen peroxide. Deletion mutagenesis in the NQO1 gene promoter identified several cis-elements including antioxidant response element (ARE), xenobiotic response element, and AP2 element, which regulate the expression and induction of the NQO1 gene. Among these DNA elements, ARE is the most important cis-element required for high basal expression of the NQO1 gene in tumor tissues, as compared to the normal tissues of the same origin, and for its induction in response to xenobiotics and antioxidants. Nucleotide sequence analysis of the ARE indicated presence of three AP1/AP1-like elements and a GCA box. Mutational analysis indicated a requirement of two AP1/AP1-like elements arranged as inverse repeats at the interval of three base pairs for the ARE activity. The GCA box in the ARE was required for optimum basal and induced expression. ARE is a novel cis-element because a single AP1/AP1-like element did not stimulate gene expression in response to xenobiotics and antioxidants. Band shift and supershift assays identified Jun, Fos, and novel proteins in the hARE-nuclear protein complexes that mediate regulation of the NQO1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Anti-inflammatory effect of triptolide].
Triptolide (Tri) was isolated from Tripterygium wilfordii Hook f. Tri 0.1-0.2 mg.kg-1 sc or 0.15-0.3 mg.kg-1 ig inhibited markedly the increased vascular permeability induced by ip 0.7% HAc in mice. Tri 0.05-0.1 mg.kg-1 ip or 0.15-0.3 mg.kg-1 ig inhibited hind paws swelling induced by sc 0.15 ml carrageenan and also inhibited the same swelling induced by sc 2.5% formaldehyde 0.1 ml in rats. Tri 0.05-0.1 mg.kg-1 ip inhibited markedly proliferation of granuloma induced by sc implantation of cotton-pellets in rats, but 0.2 mg.kg-1 ip can not inhibit the same swelling induced by sc 0.15 ml carrageenan in adrenalectomized rats. Tri 0.2 mg.kg-1 ip decreased markedly weight of thymus. Tri 0.2 mg.kg-1 ip, but 0.1 mg.kg-1 ip did not reduced the content of ascorbic acid of adrenal gland in rats. Tri 0.2 mg.kg-1 ip did not decrease the pro-staglandin E content in inflammatory tissues. These results indicate that high dose of Tri can stimulate the pituitary-adrenal axis.
Adrenal Glands↗
[Retroviral-mediated transfer of human beta-globin gene and its enhancer into MEL cells].
The present result showed that human beta-globin gene has been integrated into amphotropic packaging cell line PA317 in 5/13 clones of PA317 beta and 1/14 clone of PA317 beta E0.4. Retrovirus titers of amphotropic recombinant retrovirus ranged from 10(3) to 10(4) CFU/ml. MEL cells were transfected by supernant of PA317 beta and PA317 beta E0.4. Northern blot showed that the expression of human beta-globin gene in MEL beta E0.4 was significantly higher than MEL beta in mRNA level. This result indicated that an enhancer which comes from HS II of human LCR can increase human beta-globin gene mRNA expression in transfected MEL. However, the retrovirus titers of PA317 beta and PA317 beta E0.4 in our experiment were low. When large fragment enhancer (0.4 kb) was inserted into retrovirus vector, it could bring about the human beta-globin gene deletion in amphotropic packing cells.
Animals↗
[Leishmaniasis in Karamay. XIV. Identification of promastigote isolates from naturally infected Phlebotomus major wui].
Phlebotomus major wui, an anthropophilic species, was predominant among sandflies in Karamay, Xinjiang of China. The females of this species collected in the wild and houses were detected to be infected with promastigotes. Three isolates of promastigotes obtained from P. major wui were inoculated intraperitoneally and subcutaneously into normal hamsters or BALB/c mice which developed visceral leishmaniasis later. The mean size of amastigotes in hamster viscera (smear observation) artificially inoculated with the cultured parasite originated from sandfly was significantly smaller than those in control hamster inoculated with the cultured Leishmania turanica from great gerbils in situ. The promastigotes from P. major wui hardly grew in NNN medium. In addition, 32P labeled gene gp63 was used as probe to hybridize DNA prepared from L. infantum, L. turanica and Leishmania from this sandfly showed that marked homogeneity existed between the isolates from P. major wui and L. infantum. At the present time, visceral leishmaniasis did not occur in Karamay but cutaneous leishmaniasis (CL) has been evidenced. Thus, what is the source of natural infection of P. major wui? Whether L. turanica or L. infantum is the pathogen of human CL in this area? These are interesting aspects to deal with in the further study.
Animals↗