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Biomedical subjects

Y Liang

Publications and source records attributed to Y Liang.

At least 19 recordsLinked to original sources

Regulation of KSHV lytic gene expression.

The life cycle of KSHV, latency versus lytic replication, is mainly determined at the transcriptional regulation level. A viral immediate-early gene product, replication and transcription activator (RTA), has been identified as the molecular switch for initiation of the lytic gene expression program from latency. Here we review progress on two key questions: how RTA gene expression is controlled by viral proteins and cellular signals and how RTA regulates the expression of downstream viral genes. We summarize the interactions of RTA with cellular and other viral proteins. We also discuss critical issues that must be addressed in the near future.

Gene Expression Regulation, Viral↗

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris.

BACKGROUND AND PURPOSE: The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. EXPERIMENTAL APPROACH: The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. KEY RESULTS: In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. CONCLUSIONS AND IMPLICATIONS: The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.

Animals↗

Forced magnetic reconnection and field penetration of an externally applied rotating helical magnetic field in the TEXTOR tokamak.

The magnetic field penetration process into a magnetized plasma is of basic interest both for plasma physics and astrophysics. In this context special measurements on the field penetration and field amplification are performed by a Hall probe on the dynamic ergodic divertor (DED) on the TEXTOR tokamak and the data are interpreted by a two-fluid plasma model. It is observed that the growth of the forced magnetic reconnection by the rotating DED field is accompanied by a change of the plasma fluid rotation. The differential rotation frequency between the DED field and the plasma plays an important role in the process of the excitation of tearing modes. The momentum input from the rotating DED field to the plasma is interpreted by both a ponderomotive force at the rational surface and a radial electric field modified by an edge ergodization.

Journal Article↗

Mice expressing constitutively active Gsalpha exhibit stimulus encoding deficits similar to those observed in schizophrenia patients.

People with schizophrenia display sensory encoding deficits across a broad range of electrophysiological and behavioral measures, suggesting fundamental impairments in the ability to transduce the external environment into coherent neural representations. This inability to create basic components of complex stimuli interferes with a high fidelity representation of the world and likely contributes to cognitive deficits. The current study evaluates the effects of constitutive forebrain activation of the G(s)alpha G-protein subunit on auditory threshold and gain using acoustic brainstem responses and cortically generated N40 event-related potentials to assess the role of cyclic AMP signaling in sensory encoding. Additionally, we examine the ability of pharmacological treatments that mimic (amphetamine) or ameliorate (haloperidol) positive symptoms of schizophrenia to test the hypothesis that the encoding deficits observed in G(s)alpha transgenic mice can be normalized with treatment. We find that G(s)alpha transgenic mice have decreased amplitude of cortically generated N40 but normal acoustic brainstem response amplitude, consistent with forebrain transgene expression and a schizophrenia endophenotype. Transgenic mice also display decreased stimulus intensity response (gain) in both acoustic brainstem response and N40, indicating corticofugal influence on regions that lack transgene expression. N40 deficits in transgenic animals were ameliorated with low dose haloperidol and reversed with higher dose, suggesting dopamine D2 receptor-linked Gi activity contributes to the impairment. Consistent with this hypothesis, we recreated the G(s)alpha transgenic deficit in wild type animals using the indirect dopamine agonist amphetamine. This transgenic model of sensory encoding deficits provides a foundation for identifying biochemical contributions to sensory processing impairments associated with schizophrenia.

Acoustic Stimulation↗

A finite element simulation scheme for biological muscular hydrostats.

An explicit finite element scheme is developed for biological muscular hydrostats such as squid tentacles, octopus arms and elephant trunks. The scheme is implemented by embedding muscle fibers in finite elements. In any given element, the fiber orientation can be assigned arbitrarily and multiple muscle directions can be simulated. The mechanical stress in each muscle fiber is the sum of active and passive parts. The active stress is taken to be a function of activation state, muscle fiber shortening velocity and fiber strain; while the passive stress depends only on the strain. This scheme is tested by simulating extension of a squid tentacle during prey capture; our numerical predictions are in close correspondence with existing experimental results. It is shown that the present finite element scheme can successfully simulate more complex behaviors such as torsion of a squid tentacle and the bending behavior of octopus arms or elephant trunks.

Animals↗

The role of Foxp3+ regulatory T cells in liver transplant tolerance.

The liver has long been considered a tolerogenic organ that favors the induction of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+ regulatory T cells (Treg) in liver allograft recipients and examined the role of Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver transplant tolerance model. Orthotopic liver transplantation was performed from C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was expanded in the liver grafts and recipient spleens from day 5 up to day 100 posttransplantation, associated with high intracellular Foxp3 and CTLA4 expression. Immunohistochemistry further demonstrated significant numbers of Foxp3+ cells in the liver grafts and recipient spleens and increased transforming growth factor beta expression in the recipient spleens throughout the time courses. Adoptive transfer of spleen cells from the long-term liver allograft survivors significantly prolonged donor heart graft survival. Depletion of recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d) induced acute liver allograft rejection, associated with elevated anti-donor T-cell proliferative responses, CTL and natural killer activities, enhanced interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover, CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+ CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and apoptosis of alloreactive T cells appear to contribute to the function of Treg and regulation of graft outcome.

Animals↗

Anti-CD25 mAb administration prevents spontaneous liver transplant tolerance.

Liver allografts are accepted spontaneously in all mouse strain combinations without immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we examined the effect of CD4+ CD25+ T regulatory cells (Treg) on the induction of mouse liver transplant tolerance. Orthotopic liver transplantation was performed from B10 (H2b) to C3H (H2k) mice. Depleting rat anti-mouse CD25 mAb (PC61) was given to the donors or recipients (250 microg/d IP) pretransplant or to the recipients postoperatively. At day 5 posttransplantation, both effector T cells (mainly CD8) and CD4+ CD25+ Treg were increased in the liver allografts and host spleens compared to naïve mice. Anti-CD25 mAb administration, either pretransplantation or posttransplantation, reduced the ratio of CD4+ CD25+ Treg to the CD3 T cells of liver grafts and recipient spleens and induced liver allograft acute rejection compared to IgG treatment. Anti-CD25 mAb administration elevated anti-donor T-cell proliferative responses and CTL and NK activities of graft infiltrates and host splenocytes; reduced CTLA4, Foxp3, and IDO mRNA levels; increased IL-10 and IFN-gamma; and decreased IL-4 mRNA levels in the livers or host spleens. The number of apoptotic T cells was reduced significantly in the liver grafts and treated host spleens. Therefore, anti-CD25 mAb administration changed the balance of CD4+ CD25+ Treg to activated T cells of liver graft recipients, preventing liver transplant tolerance. This was associated with enhanced anti-donor immune reactivity, downregulated Treg gene expression, and reduced T cell apoptosis in the grafts and host spleens.

Animals↗

Schistosoma japonicum triose-phosphate isomerase plasmid DNA vaccine protects pigs against challenge infection.

The protective efficacy of a Schistosoma japonicum, Chinese strain, triose-phosphate isomerase (TPI) plasmid DNA vaccine was examined in naïve pigs. Pigs were vaccinated with the TPI DNA-plasmid alone, or in conjunction with IL-12 as pcDNA3.1-P35, pcDNA3.1-P40 plasmids via intramuscular injection. Control pigs were immunized with equivalent amounts of pcDNA3.1. Pigs were immunized 3 times at 21-day intervals and challenged 30 days after the final boost. Forty-five days post-challenge, pigs were sacrificed and perfused to compare adult worm burdens, female worm burdens, liver egg burdens and granuloma size. We found that pigs vaccinated with SjCTPI DNA alone had adult worm burdens reduced by 48.3% and that a further decrease in adult worm burdens was not seen in the group vaccinated with SjCTPI DNA in conjunction with IL-12 (46.2% reduction). The SjCTPI DNA vaccines had a more pronounced effect on reducing female worm burdens i.e. 53.6% SjCTPI alone and 59.6% for SjCTPI+IL-12. Vaccination with SjCTPI-DNA reduced liver eggs by 49.4% and this response was significantly enhanced by the addition of IL-12 (65.8% reduction in liver eggs). In addition to the dramatic protective effects seen in vaccinated pigs, we also noted that granuloma size was reduced by 42% in both groups. Thus, vaccination of pigs and other large animals in China with SjCTPI DNA vaccine will likely reduce transmission by reducing adult worm burdens and worm egg output and simultaneously reduce hepatic egg-associated pathology.

Animals↗

Association of polymorphisms in the promoter region of chicken prolactin with egg production.

Chicken prolactin (PRL) is a physiological candidate gene for egg production. The objective of the current research was to investigate the association of polymorphisms in the chicken PRL promoter region with egg production. Genotyping of 177 individuals from White Leghorn, Yangshan, Taihe Silkies, White Rock, and Nongdahe breeds for 6 single nucleotide polymorphisms (C-2402T, C-2161G, T-2101G, C-2062G, T-2054A, and G-2040A) and 1 24-bp indel (insertion-deletion) at the site of -358 of the chicken PRL gene revealed large breed differences in allelic frequencies for all but the T-2101G and T-2054A polymorphisms. An F2 population produced from Nongdahe x Taihe Silkies chickens consisted of 374 hens, which were recorded for egg production traits and genotyped for the above 7 polymorphisms. Marker-trait association analysis indicated that the 24-bp indel was associated with egg production (P < 0.01) and that H3 (C C T C T G) was the most advantageous haplotype for egg production.

Alleles↗

Defining myopia using refractive error and uncorrected logMAR visual acuity >0.3 from 1334 Singapore school children ages 7-9 years.

AIM: To determine the association of spherical equivalent (SE) with low uncorrected visual acuity (VA) along with a proposed definition for myopia using logMAR VA >0.3 as the criteria. METHODS: 1334 Chinese schoolchildren (mean age 7.8; range 7-9 years) were enrolled in the study after those who had hyperopia > or =+2.00 dioptres (D) and astigmatism > = -2.00 D were excluded. Uncorrected logMAR VA was measured for both eyes. Cycloplegia autorefraction was achieved by the instillation of three drops of 1% cyclopentolate 5 minutes apart. The average of five successful consecutive refraction and keratometry readings were obtained with calibrated Canon RK5 autokeratorefractometers by well trained optometry students, at least 30 minutes after the instillation of the third drop of cyclopentolate. SE cut-off points (-0.25 D, -0.5D, -0.75 D, -1.0 D) were evaluated. RESULTS: Using different SE cut-off points, the myopia prevalence rates of this sample of schoolchildren varied from 45.8% (SE at least -0.25 D) to 30.7% (SE at least -1.0 D). The cut-off point of > or =-0.75 D had a sensitivity and specificity of 91.8% (95% CI, 89.2 to 94.4) and 93.7% (95% CI, 92.1 to 95.3), respectively, to predict low vision defined as uncorrected logMAR VA > 0.3 (either eye). The next best cut-off point of -0.5D had a higher sensitivity (93.3%), but lower specificity (87.9%). CONCLUSIONS: The cut-off points of -0.75D and -0.5D in SE refraction are appropriate for the prediction of uncorrected logMAR VA worse than 0.3, which is the criterion for the US common state adult driver licensing standard.

Child↗

Influence of carbon and buffer amendment on ammonia volatilization in composting.

Laboratory-scale experiments were carried out to test a mathematical model of the nitrogen dynamics in a composting process. The main ingredients of composting materials were wheat straw and dairy manure. The influence of (a) two carbon amendments, i.e. molasses and office paper, and (b) two chemicals forming buffer solutions on ammonia volatilization were investigated. Nitrogen losses amounted to 12-25% of initial nitrogen, in which ammonia volatilization accounted for 60-99%. Addition of molasses, a readily available form of carbon, reduced cumulative ammonia emissions substantially, but office paper, i.e. cellulose, had only a small influence. The addition of buffering chemicals did not significantly reduce ammonia volatilization.

Alberta↗

Influence of the dynamic ergodic divertor on the density limit in TEXTOR.

A significant influence of the dynamic ergodic divertor (DED) on the density limit in TEXTOR has been found. In Ohmic discharges, where without DED detachment normally arises at the density limit, a MARFE (multifaceted asymmetric radiation from the edge) develops when the DED is operated in a static regime. The threshold of the MARFE onset in the neutral beam heated plasmas is increased by applying 1 kHz ac DED at the high-field side. The theoretical predictions based on the parallel energy balance taking poloidal asymmetries into account agree well with the experimental observation.

Journal Article↗

Toroidal plasma rotation induced by the dynamic ergodic divertor in the TEXTOR tokamak.

The first results of the Dynamic Ergodic Divertor in TEXTOR, when operating in the m/n=3/1 mode configuration, are presented. The deeply penetrating external magnetic field perturbation of this configuration increases the toroidal plasma rotation. Staying below the excitation threshold for the m/n=2/1 tearing mode, this toroidal rotation is always in the direction of the plasma current, even if the toroidal projection of the rotating magnetic field perturbation is in the opposite direction. The observed toroidal rotation direction is consistent with a radial electric field, generated by an enhanced electron transport in the ergodic layers near the resonances of the perturbation. This is an effect different from theoretical predictions, which assume a direct coupling between rotating perturbation and plasma to be the dominant effect of momentum transfer.

Journal Article↗

MRI findings of eosinophilic myelomeningoencephalitis due to Angiostrongylus cantonensis.

AIM: To study the imaging characteristics of eosinophilic myelomeningoencephalitis due to Angiostrongylus cantonensis using magnetic resonance imaging (MRI). MATERIALS AND METHODS: Seventeen MRI examinations of the brain and spinal cord in five patients with angiostrongyliasis cantonensis of the central nervous system were performed. The final diagnosis was based on typical clinical symptoms, results of blood and cerebrospinal fluid (CSF) tests, and the presence of nematode larvae in the CSF. The sequential MRI follow-up examinations were carried out at a different stage for every patient from 1 to 28 weeks after the onset of symptoms. The features of the lesions in the brain, spinal cord, meninges and nerve roots on MRI were studied, moreover, the development of the lesions was analysed on follow-up MRI. RESULTS: Abnormalities were demonstrated on MRI in all five cases. They included three cases of meningoencephalitis, one case of encephalitis and one myelomeningitis. The locations and appearances of the lesions were as follows: (1) brain involvement in four cases (including cerebrum in four, cerebellum in two and brain stem in three), and spinal cord involvement in one case. These lesions were diffuse or scattered and appeared as similar or slightly reduced signal intensity on T1-weighted images (T1WI), high signal intensity on T2-weighted images (T2WI) and turbo fluid attenuated inversion recovery pulse sequence (FLAIR) images. After administration of gadolinium chelate (Gd-DTPA), multiple round or oval enhancing nodules, with diameters ranging from 3 to 10 mm, were seen on T1WI, a few lesions appeared as stick-shaped enhancement whose longest measurement was 14 mm. Diffuse or local oedema around the lesion could be seen. (2) Meningeal involvement in four cases, a case of ependymal involvement and a case of nerve root involvement were among them. These lesions appeared as linear or nodular enhancement of the leptomeninges and ependyma, as well as nerve root enhancement. (3) There was a mild ventricular enlargement in two cases. On follow-up MRI lesions were most severe from the 5th week to the 8th week and it took at least 4-8 weeks (1-2 months) for a lesion to resolve completely, the resolution of larger lesion needed more than 22 weeks. CONCLUSION: Multiple enhancing nodules in the brain and linear enhancement in the leptomeninges were the main features; stick-shaped enhancement was the characteristic sign of the disease on Gd-DTPA enhanced-T1 weighted images.

Adult↗

Monoamine reuptake inhibition and nicotine receptor antagonism reduce amplitude and gating of auditory evoked potentials.

BACKGROUND: Sensory encoding deficits have been extensively studied as endophenotypic markers of schizophrenia using auditory evoked potentials. In order to increase understanding of the neurochemical basis of such deficits, we utilized an animal model to test whether monoamine reuptake inhibition and nicotine receptor antagonism reduce the amplitude and gating of the P20 and N40 auditory components. METHODS: C57BL/6J mice received 12 days of chronic vehicle, bupropion, haloperidol or bupropion plus haloperidol. Auditory evoked potentials were then recorded in alert mice to measure the amplitude and gating of evoked components during a paired click paradigm similar to tasks used to measure the P50 and N100 auditory potentials in schizophrenia. Evoked potentials were recorded prior to and following acute nicotine. RESULTS: Bupropion reduced the amplitude and gating of the N40 evoked potential in mice, similar to the P50 and N100 endophenotypes associated with sensory encoding deficits in schizophrenia. This deficit was fully reversed only by the combination of haloperidol and nicotine, suggesting that dopamine reuptake inhibition and nicotine antagonism both contribute to the observed phenotype. Furthermore, nicotine increased P20 amplitude across all groups supporting a role for nicotine agonists in pre-attentive sensory encoding deficits. CONCLUSIONS: We propose that the combination of monoamine inhibition and nicotine receptor antagonism may serve as a useful model for preclinical screening of pharmaceutical compounds aimed at treating sensory encoding deficits in schizophrenia.

Animals↗

Topiramate ameliorates hyperglycaemia and improves glucose-stimulated insulin release in ZDF rats and db/db mice.

Topiramate (TPM) is a novel neurotherapeutic agent. Clinical studies reported that TPM treatment reduced body weight and decreased fasting blood glucose levels in obese patients with or without type 2 diabetes. It is unclear whether the blood glucose-normalizing phenomenon observed during TPM treatment is a primary effect or the consequence of reduced food intake and weight loss. In the present studies, we chronically treated female Zucker diabetic fatty (ZDF) rats (fed with a diabetogenic diet) and db/db mice with TPM (30-300 mg/kg/day) to examine the effect of TPM on hyperglycaemia and its relationship with food intake and body weight gain. Our data showed that TPM treatment markedly reduced blood glucose levels in both ZDF rats and db/db mice without a significant reduction in body weight gain. Pair-fed db/db mice treated with the vehicle alone did not exhibit a significant decrease in blood glucose levels compared with mice fed ad libitum. TPM treatment increased glucose-stimulated insulin release by 2-3-fold during an oral glucose tolerance test in both ZDF rats and db/db mice. We also observed a 1.4-fold increase of pancreatic insulin content and heightened insulin immunostaining in pancreatic beta cells in db/db mice treated with TPM. Our data suggest that the antidiabetic effect of TPM is independent of the changes in body weight gain and food intake. Improved glucose-induced insulin release may, in part, underlie the mechanisms by which TPM ameliorates the hyperglycaemia.

Abdomen↗

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Journal Article↗

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin.

Doxorubicin- and paclitaxel-selected variants of an in vitro invasive clonal population of the human breast cancer cell line, MDA-MB-435S, were established by pulse selection, and exhibited a novel 'superinvasive' phenotype. This phenotype is characterised by an ability to relocate to another surface following invasion through matrigel and membrane pores, by decreased adhesion to extracellular matrix proteins and by increased motility. This may represent an in vitro model of a step in the metastatic process occurring subsequent to invasion. The paclitaxel-resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were resistant to paclitaxel, vincristine and docetaxel, but not to doxorubicin, carboplatin, etoposide or 5-fluorouracil. The doxorubicin-selected variants MDA-MB-435S-F/Adr-10p and MDA-MB-435S-F/Adr-10p10p, in contrast, exhibited only small increases in resistance to doxorubicin, although they were slightly resistant to VP-16 and docetaxel, and exhibited increased sensitivity to paclitaxel, carboplatin and 5-fluorouracil.

Adult↗