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Biomedical subjects

F Yang

Publications and source records attributed to F Yang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Quantitative structure-property relationship study on reductive dehalogenation of selected halogenated aliphatic hydrocarbons in sediment slurries.

In this study, by the use of partial least squares (PLS) method and 26 quantum chemical descriptors computed by PM3 Hamiltonian, a quantitative structure-property relationship (QSPR) model was developed for reductive dehalogenation rate constants of 13 halogenated aliphatic compounds in sediment slurry under anaerobic conditions. The model can be used to explain the dehalogenation mechanism. Halogenated aliphatic compounds with great energy of the lowest unoccupied molecular orbital (Elumo), total energy (TE), electronic energy (EE), the smallest bond order of the carbon-halogen bonds (BO) and the most positive net atomic charges on an atom of the molecule (q+) values tend to be reductively dehalogenated slow, whereas halogenated aliphatic compounds with high values of molecular weight (Mw), average molecular polarizability (alpha) and core-core repulsion energy (CCR) values tend to be reductively dehalogenated fastest.

Electrons↗
PubMed2001

Quantitative structure-property relationships (QSPRs) on direct photolysis of PCDDs.

By the use of partial least squares (PLS) method and 27 quantum chemical descriptors computed by PM3 Hamiltonian, a statistically significant QSPR were obtained for direct photolysis quantum yields (Y) of selected Polychlorinated dibenzo-p-dioxins (PCDDs). The QSPR can be used for prediction. The direct photolysis quantum yields of the PCDDs are dependent on the number of chlorine atoms bonded with the parent structures, the character of the carbonoxygen bonds, and molecular polarity. Increasing bulkness and polarity of PCDDs lead to decrease of log Y values. Increasing the frontier molecular orbital energies (Elumo and Ehomo) and heat of formation (HOF) values leads to increase of log Y values.

Carbon↗
PubMed2001

Multiple-label immunocytochemistry for the evaluation of nature of cell death in experimental models of neurodegeneration.

A prominent feature of neurodegenerative diseases is a loss of specific neuronal populations. The pathophysiological mechanisms responsible are, however, poorly understood. Primary cultures of rodent embryonic neurons represent a useful experimental system for investigation of molecular pathways of neurodegeneration and mechanisms of cell death. Here, we report a technique utilizing triple-label immunocytochemistry with confocal immunofluorescence detection designed to simultaneously assess multiple parameters of cell injury in individual hippocampal neurons in primary culture. This method combines detection of DNA damage (TUNEL or Klenow assay) with double-label immunocytochemistry for the activated form of caspase-3 or, alternatively, caspase-cleaved actin (fractin), and microtubule-associated protein-2 (MAP-2) or beta-tubulin. The combined evaluation of the form of nuclear damage (karyorrhexis, pyknosis), the presence or absence of activated caspase-3, and the extent of the damage to cell cytoskeleton, allows for precise assessment of the extent of injury and the mode of cell death (apoptosis, oncosis) for individual neurons.

Animals↗
PubMed2001

Karyotype relationships between distantly related marsupials from South America and Australia.

Reciprocal chromosome painting and G-banding were used to compare the karyotypes of three Australian marsupials (Sminthopsis crassicaudata, Macropus eugenii, Trichosurus vulpecula) and one South American marsupial (Monodelphis domestica). The results revealed only a limited number of rearrangements between these species and that the four karyotypes can be described as different combinations of fifteen conserved segments. Five chromosomes are totally conserved between M. domestica (pairs 1, 2, 5, 8 and the X) and the presumed 2n = 14 Australian ancestral karyotype, while M. domestica pairs 3 and 6 and 4 and 7 would have been involved in fusion/fission rearrangements. Chromosome comparisons are presented in a chromosome homology map. Although the species studied diverged 70 million years ago, the karyotype of Monodelphis domestica is highly conserved in relation to those of Australian marsupials.

Animals↗
PubMed2001

Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients.

Genetic variability in the renin angiotensin system may modify renal responses to injury and disease progression. We therefore examined whether the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, the Met235-->Thr polymorphism of the angiotensinogen (AGT) gene, and the A1166-->C polymorphism of the angiotensin II type 1 receptor gene (ATR1) were associated with disease progression and outcome after renal transplantation (Tx) in 100 Caucasian pediatric renal transplant recipients. The observed allele frequencies were: DD 31%, DI 41% and II 28%, for ACE; MM 42%, MT 37% and TT 21%, for the methionine (Met)235-->threonine (Thr) polymorphism of AGT; and AA 51%, AC 38% and CC 11%, for the adenine (A)1166-->cytosine (C) gene polymorphism. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal Tx, and the population was divided in two equal groups, according to the slope, both before and after Tx. There were no statistically significant differences for AGT, ACE, and ATR1 polymorphisms with regard to the slope of 1/creatinine before renal Tx. After renal Tx, the ACE II genotype (p = 0.024, chi-square test) and the presence of the I allele (p=0.033, chi-square test) were associated with a favorable slope of 1/creatinine. There was no association of the AGT or the ATR1 polymorphism with outcome after renal Tx, and none of the genotypes were associated with hypertension before or after renal Tx. We suggest that the beneficial association of disease progression after renal Tx with the II genotype and/or the presence of the I allele in our pediatric cohort might be explained by a lower activity of the circulating ACE enzyme associated with the I allele.

Adolescent↗
PubMed2001

PI-3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation.

Signaling mechanisms underlying neurotrophic regulation of synaptic transmission are not fully understood. Here we show that neurotrophin-3 (NT3)-induced potentiation of synaptic transmission at the neuromuscular synapses is blocked by inhibition of phosphoinositide-3 kinase, phospholipase C-gamma or the downstream IP3 receptors of phospholipase C-gamma, but not by inhibition of MAP kinase. However, neither stimulation of Ca2+ release from intracellular stores by photolysis of caged IP3, nor expression of a constitutively active phosphoinositide-3 kinase (PI3K*) in presynaptic motoneurons alone is sufficient to enhance transmission. Photo-uncaging of IP3 in neurons expressing PI3K* elicits a marked synaptic potentiation, mimicking the NT3 effect. These results reveal an involvement of PI3 kinase in transmitter release, and suggest that concomitant activation of PI3 kinase and IP3 receptors is both necessary and sufficient to mediate the NT3-induced synaptic potentiation.

Animals↗
PubMed2001

An abundance of X-linked genes expressed in spermatogonia.

Spermatogonia are the self-renewing, mitotic germ cells of the testis from which sperm arise by means of the differentiation pathway known as spermatogenesis. By contrast with hematopoietic and other mammalian stem-cell populations, which have been subjects of intense molecular genetic investigation, spermatogonia have remained largely unexplored at the molecular level. Here we describe a systematic search for genes expressed in mouse spermatogonia, but not in somatic tissues. We identified 25 genes (19 of which are novel) that are expressed in only male germ cells. Of the 25 genes, 3 are Y-linked and 10 are X-linked. If these genes had been distributed randomly in the genome, one would have expected zero to two of the genes to be X-linked. Our findings indicate that the X chromosome has a predominant role in pre-meiotic stages of mammalian spermatogenesis. We hypothesize that the X chromosome acquired this prominent role in male germ-cell development as it evolved from an ordinary, unspecialized autosome.

Animals↗
PubMed2001

GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) prevents lesion-induced death of midbrain dopaminergic neurons, but its function in normal brain remains uncertain. Here we show that GDNF acutely and reversibly potentiated the excitability of cultured midbrain neurons by inhibiting transient A-type K(+) channels. The effects of GDNF were limited to large, tyrosine hydroxylase (TH)-positive dopaminergic neurons, and were mediated by mitogen associated protein (MAP) kinase. Application of GDNF also elicited a MAP kinase-dependent enhancement of the excitability in dopaminergic neurons in midbrain slice. These results demonstrate an acute regulation of GDNF on ion channels and its underlying signaling mechanism, and reveal an unexpected role of GDNF in normal midbrain dopaminergic neurons.

4-Aminopyridine↗
PubMed2001

Leakage and aggregation of phospholipid vesicles induced by the BH3-only Bcl-2 family member, BID.

BID is a BH3 domain-only member of the Bcl-2 family that acts as an apoptotic agonist in programmed cell death. After cleavage by caspase-8, the N-terminal of BID (N-BID) stays in the cytosol while the C-terminal of BID (C-BID) translocates to mitochondria, leading to cytochrome c release in vivo and in vitro. We have previously reported that BID or truncated BID (tBID) can induce the release of entrapped trypsin and cytochrome c from large unilamellar vesicles (LUVs). Further studies have been performed and are presented here; the results demonstrate that C-BID, like BID and tBID, induces vesicle leakage, whereas N-BID or the BID mutants BID (D59A) and BID (G94E) fail to have any significant effects. The affinity of the above-mentioned proteins for soybean phospholipid LUVs (SLUVs) decreased in an order similar to their leakage-inducing capability: tBID > BID > BID (D59A), while N-BID and BID (G94E) were unable to bind to the vesicles at all. BID-induced leakage was dependent on the lipid composition of vesicles. Acidic phospholipid (e.g. phosphatidic acid or phosphatidylglycerol) was necessary for BID-induced leakage while the presence of phosphatidylethanolamine or cholesterol reduced the leakage. It was also found C-BID is better able to penetrate the soybean phospholipid monolayer than BID or tBID. A further finding was that tBID, but not full-length BID, could stimulate the aggregation of SLUVs. Finally, Bcl-x(L), an apoptotic antagonist in programmed cell death, can prevent the aggregation of LUVs induced by tBID, but not the release of entrapped trypsin. It is postulated that two separate domains of tBID are responsible for inducing leakage and aggregation of phospholipid vesicles.

BH3 Interacting Domain Death Agonist Protein↗
PubMed2001

Probing the conformational state of a truncated staphylococcal nuclease R using time of flight mass spectrometry with limited proteolysis.

The conformational state of C-terminally truncated staphylococcal nuclease R (SNR135), with and without bound ligands, has been studied by performing limited proteolysis with a specific endoproteinase Glu-C followed by electrophoresis and mass spectrometry. Comparison of the accessibility of the cleavage sites shows that the C-terminal truncation of 14 amino-acid residues causes significant unfolding of the C-terminal part of alpha helix 1 and the center of alpha helix 2, but there is little effect on other regions of the nuclease, in particular the N-terminal subdomain, which includes the active site of the nuclease. The truncation also makes the overall conformation of the nuclease more loose and flexible. Binding of ligands makes helices 1 and 2 more resistant to protease Glu-C attack and converts the partially unfolded state to a native-like state, although the conformational stability of the SNR135 complex is still much lower than that of the full-length enzyme. The results suggest that the amino-acid residues around the active site in the truncated nuclease are arranged in a similar topology to those in the full-length nuclease. The study shows that there is a clear-cut correlation between protease susceptibility and conformational stability of the protein, and the initial proteolytic events are the most critical for evaluating the conformational features of the protein. This study demonstrates how mass spectrometry can be combined with limited proteolysis to observe conformational changes induced by ligand binding.

Binding Sites↗
PubMed2001

Studies on germination conditions and antioxidant contents of wheat grain.

Germination time and conditions for wheat grain were studied to determine optimum conditions that would maximize the production of antioxidants. Wheat grains were first steeped in water for 24 or 48 h, followed by incubation in the dark for 9 d at 98% RH and 16.5 degrees C. The changes in the concentration of vitamins C and E, beta-carotene, ferulic acid and vanillic acid were monitored over the germination period. Vitamins C and E and beta-carotene were barely detectable in the dry grains. However, upon germination the concentrations of these antioxidant vitamins steadily increased with increasing germination time, reaching their peaks after 7 d at 550 mu/g for vitamin C, 10.92 micrograms/g for alpha-tocopherol, and 3.1 micrograms/g for beta-carotene. Concentrations of ferulic and vanillic acids were also increased, reaching their maxima after 7 d at 932.4 micrograms/g and 12.9 micrograms/g, respectively. The grains steeped for 48 h before germination became wet, sticky, yellow-brown color with acidic smell after 7 d. These results suggested that wheat grains steeped for 24 h and germinated for 7 d would produce the most desirable sprouts with respect to antioxidant concentrations and sensory properties.

Antioxidants↗
PubMed2001

Green tea polyphenol extract attenuates inflammation in interleukin-2-deficient mice, a model of autoimmunity.

Green tea polyphenols (GrTP) have been previously shown to decrease endotoxin-induced tumor necrosis factor-alpha production and lethality in mice. Our present studies demonstrate that GrTP inhibit inflammatory responses and may be useful in treating chronic inflammatory states, such as inflammatory bowel disease. In this preliminary study, we examined whether GrTP decrease disease activity in interleukin-2-deficient (IL-2(-/-) mice. Eight-week old IL-2(-/-) C57BL/6J mice who were fed nonpurified diet were randomly assigned to receive water with GrTP (5 g/L) or water alone (control) for up to 6 wk. After 1 wk, explant colon and lamina propria lymphocyte (LPL) cultures were established from a subgroup of mice and supernatants collected. Culture supernatants from GrTP-treated mice showed decreased spontaneous interferon-gamma and tumor necrosis factor-alpha secretion compared with that of controls. At 6 wk, the GrTP group had less severe colitis as demonstrated by lower histologic scores and wet colon weights. This was associated with lower plasma levels of serum amyloid A, increased weight gain and improved hematocrits. These results show that GrTP attenuated inflammation in IL-2(-/-) mice and suggest a role for GrTP in treating chronic inflammatory diseases such as inflammatory bowel disease.

Amyloid↗
PubMed2001

Assembly and catalysis of concerted two-end integration events by Moloney murine leukemia virus integrase.

Retroviral integration results in the stable and coordinated insertion of the two termini of the linear viral DNA into the host genome. An in vitro concerted two-end integration reaction catalyzed by the Moloney murine leukemia virus (M-MuLV) integrase (IN) was used to investigate the binding and coordination of the two viral DNA ends. Comparison of the two-end integration and strand transfer assays indicates that zinc is required for efficient concerted integration utilizing plasmid DNA as target. Complementation assays using a pair of nonoverlapping integrase domains, consisting of the HHCC domain and the core/C-terminal region, yielded products containing the correct 4-base target site duplication. The efficiency of the coordinated two-end integration varied depending on the order of addition of the individual protein and DNA components in the complementation assay. Two-end integration was most efficient when the long terminal repeat (LTR) was premixed with either the target DNA or the HHCC domain. The preference for two-end integration through preincubation of the HHCC finger with the viral DNA supports the role of this domain in the recognition and/or positioning of the LTR.

Binding Sites↗
PubMed2001

Complete genome sequence of the shrimp white spot bacilliform virus.

We report the first complete genome sequence of a marine invertebrate virus. White spot bacilliform virus (WSBV; or white spot syndrome virus) is a major shrimp pathogen with a high mortality rate and a wide host range. Its double-stranded circular DNA genome of 305,107 bp contains 181 open reading frames (ORFs). Nine homologous regions containing 47 repeated minifragments that include direct repeats, atypical inverted repeat sequences, and imperfect palindromes were identified. This is the largest animal virus that has been completely sequenced. Although WSBV is morphologically similar to insect baculovirus, the two viruses are not detectably related at the amino acid level. Rather, some WSBV genes are more homologous to eukaryotic genes than viral genes. In fact, sequence analysis indicates that WSBV differs from all known viruses, although a few genes display a weak homology to herpesvirus genes. Most of the ORFs encode proteins that bear no homology to any known proteins, either suggesting that WSBV represents a novel class of viruses or perhaps implying a significant evolutionary distance between marine and terrestrial viruses. The most unique feature of WSBV is the presence of an intact collagen gene, a gene encoding an extracellular matrix protein of animal cells that has never been found in any viruses. Determination of the genome of WSBV will facilitate a better understanding of the molecular mechanism underlying the pathogenesis of the WSBV virus and will also provide useful information concerning the evolution and divergence of marine and terrestrial animal viruses at the molecular level.

Amino Acid Sequence↗
PubMed2001

Phylogenetic implications of the 38 putative ancestral chromosome segments for four canid species.

Chromosome homologies between the Japanese raccoon dog (Nectereutes procyonoides viverrinus, 2n = 39 + 2-4 B chromosomes) and domestic dog (Canis familiaris, 2n = 78) have been established by hybridizing a complete set of canine paint probes onto high-resolution G-banded chromosomes of the raccoon dog. Dog chromosomes 1, 13, and 19 each correspond to two raccoon dog chromosome segments, while the remaining 35 dog autosomes each correspond to a single segment. In total, 38 dog autosome paints revealed 41 conserved segments in the raccoon dog. The use of dog painting probes has enabled integration of the raccoon dog chromosomes into the previously established comparative map for the domestic dog, Arctic fox (Alopex lagopus), and red fox (Vulpes vulpes). Extensive chromosome arm homologies were found among chromosomes of the red fox, Arctic fox, and raccoon dog. Contradicting previous findings, our results show that the raccoon dog does not share a single biarmed autosome in common with the Arctic fox, red fox, or domestic cat. Comparative analysis of the distribution patterns of conserved chromosome segments revealed by dog paints in the genomes of the canids, cats, and human reveals 38 ancestral autosome segments. These segments could represent the ancestral chromosome arms in the karyotype of the most recent ancestor of the Canidae family, which we suggest could have had a low diploid number, based on comparisons with outgroup species.

Animals↗
PubMed2001

Conserved chromosome segments in Hylobates hoolock revealed by human and H. leucogenys paint probes.

A complete comparative chromosome map of the white-browed gibbon (Hylobates hoolock, 2n = 38), white-cheeked gibbon (Hylobates leucogenys, 2n = 52), and human has been established by hybridising H. leucogenys chromosome-specific paints and human 24-colour paints onto H. hoolock metaphase chromosomes. In the 18 H. hoolock autosomes, we identified 62 conserved segments that showed DNA homology to regions of the 25 H. leucogenys autosomes. Numerous interchromosomal rearrangements differentiate the karyotypes of H. leucogenys and H. hoolock. Only H. hoolock chromosome 10 showed homology to one entire autosome of H. leucogenys. The hybridisation of human 24-colour paints not only confirmed most of the chromosome correspondences between human and H. hoolock established previously but also helped to correct five erroneous assignments and revealed three new segments. Our results demonstrate that the karyotypes of the extant gibbons have arisen mainly through extensive translocation events and that the karyotype of H. hoolock more closely resembles the ancestral karyotype of Hylobates, rather than the karyotype of H. leucogenys.

Animals↗
PubMed2001

Antifibrotic effects of N-acetyl-seryl-aspartyl-Lysyl-proline on the heart and kidney in aldosterone-salt hypertensive rats.

N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) inhibits not only hematopoietic cell proliferation but also fibroblast proliferation and collagen synthesis in vitro. Ac-SDKP also prevents collagen deposition and cell proliferation in the left ventricle (LV) in rats with renovascular hypertension (renin dependent). However, it is not clear whether Ac-SDKP has similar effects in a model of renin-independent hypertension (aldosterone-salt). Using a hypertensive rat model of cardiac and renal fibrosis created by chronic elevation of circulating aldosterone (ALDO) levels, we examined the effect of Ac-SDKP on blood pressure, cardiac and renal fibrosis and hypertrophy, and proliferating cell nuclear antigen (PCNA) expression in the LV and left kidney. Uninephrectomized rats were divided into 4 groups: (1) controls that received tap water, (2) rats that received ALDO (0.75 microgram/h SC) and 1% NaCl/0.2% KCl in drinking water (ALDO-salt), (3) rats that received ALDO-salt plus Ac-SDKP 400 microgram. kg(-1). day(-1) SC, and (4) rats that received ALDO-salt plus Ac-SDKP 800 microgram. kg(-1). d(-1) SC. After 6 weeks of treatment, the ALDO-salt group was found to have significantly increased blood pressure with decreased body weight and plasma renin concentration (P<0.05), LV and renal hypertrophy as well as renal injury, significantly increased collagen content in both ventricles and kidney as well as increased collagen volume fraction in the LV (P<0.0001), and significantly increased interstitial and perivascular PCNA-positive cells in the LV and kidney (P<0.0001). Ac-SDKP at 800 microgram. kg(-1). d(-1) markedly prevented cardiac and renal fibrosis (P<0.005) without affecting blood pressure or organ hypertrophy. It also suppressed PCNA expression in the LV and kidney in a dose-dependent manner. We concluded that Ac-SDKP prevents increased collagen deposition and cell proliferation in the heart and kidney in ALDO-salt hypertensive rats. Because ACE inhibitors increase plasma and tissue Ac-SDKP and decrease cardiac and renal fibrosis, we speculate that Ac-SDKP may participate in the antifibrotic effect of ACE inhibitors.

Aldosterone↗