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Biomedical subjects

L Liu

Publications and source records attributed to L Liu.

At least 109 records · Page 6Linked to original sources

Inheritance and fine mapping of fertility restoration for cytoplasmic male sterility in Gossypium hirsutum L.

Genetics of CMS fertility restoration was presented through the analysis of classic genetics and molecular markers. Based on F(2) segregation of the crosses between CMS and the restoring lines, the testcrosses and F(1) x F(1) populations, together with RAPD and SSR mapping, one dominant gene was identified to control the CMS fertility restoration in cotton. The strategy of genotype representation analysis (GRA) was put forward to screen the markers linked with the Rf(1) locus. Using 1,025 random decamer primers and 282 pairs of SSR primers, two RAPD and three SSR markers were identified to be closely linked to the Rf(1) gene. Among the five markers, three were co-dominantly inherited. Additionally, based on the analysis of monosomic and telesomic lines with one SSR maker, the Rf(1) locus could be located on the long arm of chromosome 4. The molecular markers available here are helpful in the development of the elite restoring lines in cotton by marker-assisted selection.

Chromosome Mapping↗

Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells.

Wnt-1, the vertebrate counterpart of the Drosophila wingless gene, plays an important role in the early morphogenesis of neural tissues. In this report, we have shown that overexpression of Wnt-1 can direct embryonic carcinoma P19 cells to differentiate into neuron-like cells in the absence of retinoic acid. Immunocytochemistry showed that these cells expressed neuronal markers, such as the neurofilament (NF) and microtubule-associated protein 2 (MAP2), but failed to express the glial cell marker, glial fibrillary acidic protein (GFAP). RT-PCR revealed that two basic helix-loop-helix (bHLH) genes, Mash-1 and Ngn-1, were up-regulated during the differentiation stage of Wnt-1-overexpressing P19 cells. These results suggest that the Wnt-1 gene promotes neuronal differentiation and inhibits gliogenesis during the neural differentiation of P19 cells, and that neural bHLH genes might be involved in this process.

Animals↗

Rotational dynamics of hydration water in dicalcium silicate by quasielastic neutron scattering.

Quasielastic neutron scattering (QENS) has been used to investigate the single-particle dynamics of interfacial water in dicalcium silicate (C2S)/water paste. Our previous neutron-scattering studies on interfacial water have focused attention on the translational dynamics of the center of mass of water molecules. In this paper, we have collected QENS data on a wider range of wave-vector transfer so that both translational and rotational motions of water molecules are detected. The data have been analyzed by models for translation and rotation we recently proposed for supercooled water. The evolution of the parameters describing the relaxational dynamics of water embedded in the C2S matrix is given at temperature T=303 K as a function of the curing time.

Journal Article↗

A cat cloned by nuclear transplantation.

Sheep, mice, cattle, goats and pigs have all been cloned by transfer of a donor cell nucleus into an enucleated ovum, and now we add the successful cloning of a cat (Felis domesticus) to this list. However, this cloning technology may not be readily extendable to other mammalian species if our understanding of their reproductive processes is limited or if there are species-specific obstacles.

Animals↗

Regulation of sarco/endoplasmic Ca2+ -ATPase expression by calcium in human lens cells.

Maintenance of cellular calcium levels is critical to cell function. Loss of calcium homeostasis might be a contributing factor to the development of cataract in the lens. In lens epithelium, calcium is involved in cell signaling and its precise regulation is vital. In this study, we investigated the regulation of sarco/endoplasmic reticulum Ca(2+)-ATPase2b (SERCA2b) and SERCA3 isoform expression in cultured epithelial B-3 cells from human lenses. Both mRNA and membrane proteins samples were collected for semi quantitative RT-PCR using GAPDH as a control. Western blot analyses were performed on membrane samples.Thapsigargin, a SERCA isoform inhibitor which causes increased cytosolic levels elicited dose-and time-dependent up-regulation of SERCA3 at both mRNA and protein levels; SERCA2b expression was unaffected. Both EGTA and actinomycin partially inhibited the thapsigargin-induced SERCA3 up-regulation. These results indicate that the up-regulation of SERCA3 by thapsigargin is dependent on a calcium-mediated pathway that is likely to occur at the transcription level.

Blotting, Western↗

The effects of long-term treatment with metrifonate, a cholinesterase inhibitor, on cholinergic activity, amyloid pathology, and cognitive function in APP and PS1 doubly transgenic mice.

Recent studies in cell cultures have shown that modulating the cholinergic activity can influence the processing and metabolism of amyloid precursor protein (APP). To investigate whether acetylcholinesterase inhibitors (ChEIs) could decrease production of amyloid beta-peptide (A(beta)) and slow down the accumulation of A(beta) also in vivo, we chronically administered metrifonate (100 mg/kg, po), a second-generation ChEI, to 7-month-old doubly transgenic APP+PS1 mice and their nontransgenic littermate controls for 7 months. Behavioral studies, including open field test, T maze, and water maze, were conducted after 6 months treatment with metrifonate, and the mice were sacrificed at the age of 14 months for biochemical and histological analyses. The long-term treatment with metrifonate failed to inhibit the marked overproduction and deposition of A(beta) in the APP+PS1 mice; in contrast, it increased both A(beta)40 and A(beta)42 levels in the hippocampus. However, the A(beta)42 to 40 ratio was significantly reduced by the treatment. In addition, the number of amyloid plaques in the hippocampus did not differ between the treatment and the control groups. Tolerance to cholinesterase inhibition might be induced in the mouse brain because the inhibition rate of AChE was attenuated from about 80 to 50% during the experiment in both APP+PS1 and nontransgenic mice. The metrifonate treatment did not affect cognitive testing parameters but reduced swimming speed and locomotor activity in both genotypes. Our results do not support the idea that ChEIs would slow down the progression of amyloid pathology in Alzheimer's disease.

Alzheimer Disease↗

Oxidative stress and metallothionein expression in the liver of rats with severe thermal injury.

The aim of this work was to study oxidative stress and the compensating mechanisms implicated in severe thermal injury using the burned rat model. Results showed that after thermal injury glutathione (GSH) level was decreased, oxidized glutathione (GSSG) and the ratio of GSSG/GSH increased both at 24 and 48 h in the liver. The activities of GSH-reductase (GSH-Rx) in the liver and GSH-peroxidase (GSH-Px) both in the liver and erythrocytes increased at 24 h and then decreased at 48 h. The level of alpha-tocopherol in plasma was reduced at 24 h. Lipid peroxide levels increased both at 24 and 48 h in the liver. The serum zinc level decreased, reaching a minimum at 12h, whereas liver zinc level was elevated and reached the maximum at 12 h. After severe thermal injury enhancement of metallothionein (MT) expression has been discovered for the first time. MT content in the liver increased both at 24 and 48 h. Expression of MT-I mRNA was activated at 3 h and reached the top at 24 h postburn. The conclusion is that severe thermal injury gives rise to oxidative stress and dramatic enhancement of MT expression could be one of the important compensative mechanisms of natural defense system postburn.

Animals↗

Analysis of intra-operative bleeding and recurrence of juvenile nasopharyngeal angiofibromas.

The purpose of this study is to present our experience with 34 patients diagnosed with juvenile nasopharyngeal angiofibromas and treated in the Chinese PLA General Hospital between 1986 and 1999, and to examine the factors influencing intra-operative bleeding and tumour recurrence. The age of the patient, the duration of symptoms and tumour stage were related to the amount of intra-operative bleeding. The tumours were totally resected in 30 patients and recurred in five patients (16.7%), with a mean follow-up time of 77 months. The mean time to tumour recurrence after operation was 3.2 months (1-6 months). The incidence of recurrence had no correlation with the age of the patient, duration of symptoms, peri-operative treatment or surgical approaches (P > 0.05); but strongly correlated with tumour stage (P < 0.05).

Adolescent↗

Isolation of various forms of sterol beta-D-glucoside from the seed of Cycas circinalis: neurotoxicity and implications for ALS-parkinsonism dementia complex.

The factors responsible for ALS-parkinsonism dementia complex (ALS-PDC), the unique neurological disorder of Guam, remain unresolved, but identification of causal factors could lead to clues for related neurodegenerative disorders elsewhere. Earlier studies focused on the consumption and toxicity of the seed of Cycas circinalis, a traditional staple of the indigenous diet, but found no convincing evidence for toxin-linked neurodegeneration. We have reassessed the issue in a series of in vitro bioassays designed to isolate non-water soluble compounds from washed cycad flour and have identified three sterol beta-d-glucosides as potential neurotoxins. These compounds give depolarizing field potentials in cortical slices, induce alterations in the activity of specific protein kinases, and cause release of glutamate. They are also highly toxic, leading to release of lactate dehydrogenase (LDH). Theaglycone form, however, is non-toxic. NMDA receptor antagonists block the actions of the sterol glucosides, but do not compete for binding to the NMDA receptor. The most probable mechanism leading to cell death may involve glutamate neuro/excitotoxicity. Mice fed cycad seed flour containing the isolated sterol glucosides show behavioral and neuropathological outcomes, including increased TdT-mediated biotin-dUTP nick-end labelling (TUNEL) positivity in various CNS regions. Astrocytes in culture showed increased caspase-3 labeling after exposure to sterol glucosides. The present results support the hypothesis that cycad consumption may be an important factor in the etiology of ALS-PDC and further suggest that some sterol glucosides may be involved in other neurodegenerative disorders.

Amyotrophic Lateral Sclerosis↗

[The human alpha(2A)-AR gene and the genotype of site -1296 and the susceptibility to motion sickness].

The gene sequences of alpha(2A)-adrenergic receptor(alpha(2A)-AR) in 39 Chinese and 1 Englishman showed 13 differences of g or c insertion or deletion in its regulation region, coding region and 3' untranslated region, compared with that reported in GenBank. The gene sequences from all the samples respectively were identical except for 2 single nucleotide polymorphisms, including the sequence of sense and antisense strand sequenced. It was found that: (1) the frequency of gg genotype in Chinese and Japanese, who are high susceptible to motion sickness, were 5.8 and 7.8 fold higher than that in Englishmen; (2) g allele frequencies in Chinese and Japanese were higher than latter ( P 0.01 ); (3) gg genotype frequency in population susceptible to motion sickness was 1.6 fold higher than that in population unsusceptible to motion sickness, and g allele frequency was higher than latter ( P 0.01 ). All the populations were in Hardy-Weinberg equilibrium. The results suggested that gg genotype and g allele at site -1296 in alpha(2A)-AR gene could associate with the susceptibility to motion sickness.

Asian People↗

Estimation of atmospheric mixing heights over large areas using data from airport meteorological stations.

For this study, ground and sounding meteorological data at 16 airports were used for estimating the atmospheric mixing heights in Hebei Province of China, including Beijing and Tanjing areas. Three methods were compared for this purpose, which are the dry adiabatic method, the conventional Nozaki model, and a modified Nozaki model. The feasibility of using airport meteorological data to determine mixing heights in large area was verified through the use of measured mixing heights and observed SO2 vertical profiles. The study not only estimated the mixing heights over large areas but also compared different early morning sounding temperature profiles to identify feasibility of using 2:00 a.m. sounding profiles to estimate mixing height by the dry adiabatic method. The paper also described the mixing heights over different areas such as mountain, sea boundary and plain areas. The results have considerable significance for air quality prediction and environmental management. A novel approach to estimation of atmospheric mixing heights over large area is introduced, requiring only the input of readily available airport meteorological data.

Air Movements↗

Violation analysis for solid waste management systems: an interval fuzzy programming approach.

This paper introduces a violation analysis approach for the planning of regional solid waste management systems under uncertainty, based on an interval-parameter fuzzy integer programming (IPFIP) model. In this approach, several given levels of tolerable violation for system constraints are permitted. This is realized through a relaxation of the critical constraints using violation variables, such that the model's decision space can be expanded. Thus, solutions from the violation analysis will not necessarily satisfy all of the model's original constraints. Application of the developed methodology to the planning of a waste management system indicates that reasonable solutions can be generated through this approach. Considerable information regarding decisions of facility expansion and waste flow allocation within the waste management system were generated. The modeling results help to generate a number of decision alternatives under various system conditions, allowing for more in-depth analyses of tradeoffs between environmental and economic objectives as well as those between system optimality and reliability.

Fuzzy Logic↗

Acidic stimuli activates two distinct pathways in taste receptor cells from rat fungiform papillae.

A sour taste sensation may be produced when acidic stimuli interact with taste receptor cells (TRCs) on the dorsal surface of the tongue. We have searched for pathways in TRCs that may be activated by acidic stimuli using RT-PCR and changes in intracellular calcium (Ca(2+)(I)) induced by acidic stimuli in rat fungiform papillae. RT-PCR revealed the presence of proton-gated subunits ASIC-beta and VR1. Ca(2+) imaging measurements of the TRCs revealed two distinct responses to acidic stimuli: Ca(2+)(i) was increased in 9% (28/308; Type I) and was decreased in 39% (121/308; Type II). Neither of these responses was affected by the removal of extracellular Ca(2+), indicating that the changes arise from the release and sequestration of Ca(2+) from intracellular stores. These responses were also not inhibited by the vanilloid receptor antagonist, capsazepine, suggesting they do not arise from the activation of vanilloid receptors. The Type I, but not the Type II response was inhibited by amiloride. Dose-response measurements for Types I and II responses yielded pH(50%) of 4.8 and 4.9, respectively. Type II responses were inhibited by pertussis toxin, suggesting G-protein involvement. TRCs that exhibit Type II responses could also be activated by quinine (which increased Ca(2+)(I)) thus suggesting a mechanism by which the addition of acid may be suppressive to other chemical stimuli.

Acid Sensing Ion Channels↗

Members of a dinoflagellate luciferase gene family differ in synonymous substitution rates.

Regulation and evolution of dinoflagellate luciferases are of particular interest since the enzyme is structurally unique and bioluminescence is under circadian control. In this study, three new members of the dinoflagellate luciferase gene family were identified and characterized from Pyrocystis lunula. These genes, lcfA, lcfB, and lcfC, also exhibit the unusual structure and organization previously reported for the luciferase gene of a related dinoflagellate, Lingulodinium polyedrum: three repeated domains, each encoding an active catalytic site, multiple gene copies, and tandem organization. The histidine residues involved in the pH regulation of L. polyedrum luciferase activity, and implicated in the regulation of flashing, are also fully conserved in P. lunula. The interspecific conservation between the individual luciferase domains of P. lunula and L. polyedrum is higher than among domains intramolecularly, indicating that this unique gene structure arose through duplication events that occurred prior to the divergence of these dinoflagellates. However, P. lunula luciferase genes differ from L. polyedrum in several respects, notably, the occurrence of an intron in one gene (lcfC), a 2.25-kb intergenic region connecting lcfA and lcfB, and, of particular interest, an invariant rate of synonymous (silent) substitutions along the repeat domains, in contrast to L. polyedrum luciferase, where the occurrence of synonymous substitutions is practically absent in the central region of the domains.

Amino Acid Sequence↗

Subsite-specific incidence rate and stage of disease in colorectal cancer by race, gender, and age group in the United States, 1992-1997.

BACKGROUND: Subsite specific incidence rates of colorectal cancer vary considerably by age, gender, and race. This variation may be related not only to distinctions in exposure to genetic and environment factors but also to current strategies of early detection screening. Patterns of stage of disease in anatomic subsite may reflect the effect of screening. This study used the largest aggregation of cancer incidence data in the U.S. to examine subsite specific incidence rates of colorectal cancer and the relation of stage of disease to anatomic subsites by race, gender, and age group. METHODS: Data on the incidence of invasive colorectal cancer were obtained from 28 population-based central cancer registries. Age-specific and age-adjusted rates and stage distributions were analyzed by subsite, race, and gender. RESULTS: The impact of screening can be observed in the percentage of localized disease, which increased from 31.9% among cancers in the proximal colon to 37.0% in the descending colon to 41.5% in the distal colorectum. Within the same subsite, blacks were less likely than whites to receive a diagnosis of localized disease and more likely to receive a diagnosis of distant disease whereas stage distributions were approximately the same for males and females. Blacks were more likely than whites to receive a diagnosis of proximal colon cancer than distal colorectal cancer. The male-to-female rate ratios progressively increased from the proximal colon to the distal colorectum. The ratios of proximal-to-distal colorectal cancer gradually increased with advancing age. CONCLUSIONS: Differentials in stage of disease by subsites indicate a need for a targeted effort at early detection of cancer in the proximal colon. Risk factors and higher risk populations for colorectal cancers in each subsite need to be studied further to guide actions for improving the efficacy of screening.

Age Factors↗

Exploiting subsite S1 of trypsin-like serine proteases for selectivity: potent and selective inhibitors of urokinase-type plasminogen activator.

A nonselective inhibitor of trypsin-like serine proteases, 2-(2-hydroxybiphenyl-3-yl)-1H-indole-5-carboxamidine (1) (Verner, E.; Katz, B. A.; Spencer, J.; Allen, D.; Hataye, J.; Hruzewicz, W.; Hui, H. C.; Kolesnikov, A.; Li, Y.; Luong, C.; Martelli, A.; Radika. K.; Rai, R.; She, M.; Shrader, W.; Sprengeler, P. A.; Trapp, S.; Wang, J.; Young, W. B.; Mackman, R. L. J. Med. Chem. 2001, 44, 2753-2771) has been optimized through minor structural changes on the S1 binding group to afford remarkably selective and potent inhibitors of urokinase-type plasminogen activator (uPA). The trypsin-like serine proteases(1) that comprise drug targets can be broadly categorized into two subfamilies, those with Ser190 and those with Ala190. A single-atom modification, for example, replacement of hydrogen for chlorine at the 6-position of the 5-amidinoindole P1 group on 1, generated up to 6700-fold selectivity toward the Ser190 enzymes and against the Ala190 enzymes. The larger chlorine atom displaces a water molecule (H(2)O1(S1)) that binds near residue 190 in all the complexes of 1, and related inhibitors, in uPA, thrombin, and trypsin. The water molecule, H(2)O1(S1), in both the Ser190 or Ala190 enzymes, hydrogen bonds with the amidine N1 nitrogen of the inhibitor. When it is displaced, a reduction in affinity toward the Ala190 enzymes is observed due to the amidine N1 nitrogen of the bound inhibitor being deprived of a key hydrogen-bonding partner. In the Ser190 enzymes the affinity is maintained since the serine hydroxyl oxygen O gamma(Ser190) compensates for the displaced water molecule. High-resolution crystallography provided evidence for the displacement of the water molecule and validated the design rationale. In summation, a novel and powerful method for engineering selectivity toward Ser190 proteases and against Ala190 proteases without substantially increasing molecular weight is described.

Amidines↗