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Biomedical subjects

Y Hong

Publications and source records attributed to Y Hong.

At least 91 records · Page 5Linked to original sources

A genetic study of sex hormone--binding globulin measured before and after a 20-week endurance exercise training program: the HERITAGE Family Study.

Familial aggregation and a major gene effect were assessed for baseline serum sex hormone-binding globulin (SHBG) levels and the response (post-training minus baseline) to a 20-week endurance training program in a selected sample of 428 non-obese nonhypertensive individuals from 99 white families who were sedentary at baseline in the HERITAGE Family Study. Baseline SHBG levels were not normally distributed, and were therefore logarithmically transformed prior to genetic analyses. In a sample without postmenopausal mothers, maximal (genetic and familial environmental) heritabilities were 50% averaged across sexes, 73% in men, 50% in women, and 31% in men versus women for the age-body mass index (BMI)-adjusted baseline. The estimate reached 64% when the baseline was further adjusted for the effects of estradiol, fasting insulin, and testosterone levels. For the response to training, no sex difference was found and the heritability reached about 25% to 32%. Segregation analysis was separately performed in the whole sample and in the sample without postmenopausal mothers. In addition to a multifactorial effect for both the baseline and the response to training, a major effect for the baseline appeared to be familial environmental in origin, whereas a major effect for the response to training was Mendelian in nature. The major gene effect for the response to training in the whole sample was undetectable in the sample without postmenopausal mothers, and it is therefore possible that the postmenopausal mothers, characterized by decreased sex hormones with or without estrogen replacement therapy for menopause, produced some confounding effects. In addition, the reduced sample size might also be a plausible candidate explanation. The novel finding in this study is that baseline SHBG levels and the response to training were influenced by a multifactorial effect with sex difference for the baseline. The response to training appeared to be additionally influenced by a single recessive locus that is independent of baseline SHBG levels.

Adult↗

Effects of load carriage on heart rate, blood pressure and energy expenditure in children.

Fifteen male primary school children, aged 10 years, were selected to carry school bags of 10, 15 and 20% of their own body weights, where 0% body weight was used as a control. Maximum oxygen uptake (VO2max) tests were conducted on a motorized treadmill using a continuous incremental protocol. During the load carrying test, subjects walked on a treadmill at 1.1 m s(-1) for 20 min at each load condition. Blood pressures were measured before, immediately following, and at 3 and 5 min after every trial. Heart rate and expired VO2 were recorded before, during and 5 min after walking using a cardiopulmonary function system. The results showed a significant difference in oxygen uptake, energy expenditure and the recovery of blood pressure rise for between 10 and 20% body weight load conditions. The carrying weight of a school bag for children could be recommended as 10% of body weight because it was not significantly different from 0% load in the metabolic cost.

Biomechanical Phenomena↗

Essential functions of protein tyrosine phosphatases PTP2 and PTP3 and RIM11 tyrosine phosphorylation in Saccharomyces cerevisiae meiosis and sporulation.

Tyrosine phosphorylation plays a central role in eukaryotic signal transduction. In yeast, MAP kinase pathways are regulated by tyrosine phosphorylation, and it has been speculated that other biochemical processes may also be regulated by tyrosine phosphorylation. Previous genetic and biochemical studies demonstrate that protein tyrosine phosphatases (PTPases) negatively regulate yeast MAP kinases. Here we report that deletion of PTP2 and PTP3 results in a sporulation defect, suggesting that tyrosine phosphorylation is involved in regulation of meiosis and sporulation. Deletion of PTP2 and PTP3 blocks cells at an early stage of sporulation before premeiotic DNA synthesis and induction of meiotic-specific genes. We observed that tyrosine phosphorylation of several proteins, including 52-, 43-, and 42-kDa proteins, was changed in ptp2Deltaptp3Delta homozygous deletion cells under sporulation conditions. The 42-kDa tyrosine-phosphorylated protein was identified as Mck1, which is a member of the GSK3 family of protein kinases and previously known to be phosphorylated on tyrosine. Mutation of MCK1 decreases sporulation efficiency, whereas mutation of RIM11, another GSK3 member, specifically abolishes sporulation; therefore, we investigated regulation of Rim11 by Tyr phosphorylation during sporulation. We demonstrated that Rim11 is phosphorylated on Tyr-199, and the Tyr phosphorylation is essential for its in vivo function, although Rim11 appears not to be directly regulated by Ptp2 and Ptp3. Biochemical characterizations indicate that tyrosine phosphorylation of Rim11 is essential for the activity of Rim11 to phosphorylate substrates. Our data demonstrate important roles of protein tyrosine phosphorylation in meiosis and sporulation

DNA, Fungal↗

Familiality of triglyceride and LPL response to exercise training: the HERITAGE study.

PURPOSE: The main purpose of the present investigation was to test whether and to what extent familial/genetic factors are involved in the changes of postheparin lipoprotein lipase (deltaPH-LPL) activity and triglyceride (deltaTG) levels in response to exercise training. Additional hypotheses were also tested as to whether there were familial/genetic factors shared by baseline and the corresponding response to exercise training (i.e., by baseline triglyceride (TG(B)) and deltaTG and by baseline postheparin lipoprotein lipase (PH-LPL(B)) and deltaPH-LPL activity). METHODS: Serum TG and PH-LPL were measured in 459 subjects from 99 sedentary Caucasian families of the HERITAGE Family study before (baseline) and after completing a 20 wk (3 times per week) exercise training protocol. The training protocol had a target intensity of 75% of the heart rate associated with baseline VO2max during the last 6 wk. PH-LPL activity was measured in the study subjects. Both univariate and bivariate familial correlation analyses were applied to the baseline and response data. RESULTS: The maximal heritabilities for deltaTG and deltaPH-LPL activity were 22% and 15%, respectively. There were no common familial factors for TG(B) and deltaTG, nor were there any for PH-LPL(B) and deltaPH-LPL. However, we found that there were common familial factors underlying deltaTG and deltaPH-LPL; these familial factors seemed to differ across sex and generation groups. CONCLUSION: Although there were no common familial factors underlying the covariation between the baseline triglyceride and PH-LPL activity and the corresponding responses to exercise training (i.e., TG(B) with deltaTG or PH-LPL(B) with deltaPH-LPL), the deltaTG and deltaPH-LPL covariation apparently share some common familial determinants.

Adolescent↗

Transactivation activity of the human cytomegalovirus IE2 protein occurs at steps subsequent to TATA box-binding protein recruitment.

The IE2 protein of human cytomegalovirus transactivates viral and cellular promoters through a wide variety of cis-elements, but the mechanism of its action has not been well characterized. Here, IE2-Sp1 synergy and IE2-TATA box-binding protein (TBP) interaction are examined by artificial recruitment of either Sp1 or TBP to the promoter. It was found that IE2 could cooperate with DNA-bound Sp1. A 117 amino acid glutamine-rich fragment of Sp1, which can interact with Drosophila TAF(II)110 and human TAF(II)130, was sufficient for the augmentation of IE2-driven transactivation. In binding assays in vitro, IE2 interacted directly with the C-terminal region of Sp1, which contains the zinc finger DNA-binding domain, but not with its transactivation domain, suggesting that synergy between IE2 and the transactivation domain of Sp1 might be mediated by other proteins such as TAF or TBP. It was also found that TBP recruitment to the promoter markedly increased IE2-mediated transactivation. Thus, IE2 acts synergistically with DNA-bound Sp1 and DNA-bound TBP. These results suggest that, in human cytomegalovirus IE2 transactivation, Sp1 functions at an early step such as recruitment of TBP and IE2 acts to accelerate rate-limiting steps after TBP recruitment.

Animals↗

Phylogenetic analysis by rRNA comparison of the highly pathogenic sheep-infecting parasites Theileria lestoquardi and a Theileria species identified in China.

In the Northwestern part of China there have been reports of clinical cases in small ruminants of a haemoparasite with the characteristics of Theileria hirci (T. lestoquardi). However, some properties of this parasites argue against its classification as T. lestoquardi. In this paper, we present evidence that T. lestoquardi and the Chinese Theileria isolate are distinct parasite species. Phylogenetic analysis of determined nucleotide sequences of small subunit ribosomal RNA (srRNA) genes of T. lestoquardi and the Chinese Theileria parasite show that they belong to different clades within the phylogenetic tree of piroplasms. The srRNA sequence of the Chinese parasite was found to be most closely related to T. buffeli, which, with T. sergenti, belongs to an evolutionary lineage of non-lymphoproliferative Theileria species. On the other hand, it was clearly divergent to a lineage of lymphoproliferative Theileria species; T. annulata, T. parva, T. taurotragi, and T. lestoquardi, the latter being most closely related to T. annulata.

Animals↗

Structure and function analysis of LIN-14, a temporal regulator of postembryonic developmental events in Caenorhabditis elegans.

During postembryonic development of Caenorhabditis elegans, the heterochronic gene lin-14 controls the timing of developmental events in diverse cell types. Three alternative lin-14 transcripts are predicted to encode isoforms of a novel nuclear protein that differ in their amino-terminal domains. In this paper, we report that the alternative amino-terminal domains of LIN-14 are dispensable and that a carboxy-terminal region within exons 9 to 13 is necessary and sufficient for in vivo LIN-14 function. A transgene capable of expressing only one of the three alternative lin-14 gene products rescues a lin-14 null mutation and is developmentally regulated by lin-4. This shows that the deployment of alternative lin-14 gene products is not critical for the ability of LIN-14 to regulate downstream genes in diverse cell types or for the in vivo regulation of LIN-14 level by lin-4. The carboxy-terminal region of LIN-14 contains an unusual expanded nuclear localization domain which is essential for LIN-14 function. These results support the view that LIN-14 controls developmental timing in C. elegans by regulating gene expression in the nucleus.

Amino Acid Sequence↗

Balance control, flexibility, and cardiorespiratory fitness among older Tai Chi practitioners.

BACKGROUND: Tai Chi Chuan (TTC) exercise has beneficial effects on the components of physical condition and can produce a substantial reduction in the risk of multiple falls. Previous studies have shown that short term TCC exercise did not improve the scores in the single leg stance test with eyes closed and the sit and reach test. There has apparently been no research into the effects of TCC on total body rotation flexibility and heart rate responses at rest and after a three minute step test. METHODS: In this cross sectional study, 28 male TCC practitioners with an average age of 67.5 years old and 13.2 years of TCC exercise experience were recruited to form the TCC group. Another 30 sedentary men aged 66.2 were selected to serve as the control group. Measurements included resting heart rate, left and right single leg stance with eyes closed, modified sit and reach test, total body rotation test (left and right), and a three minute step test. RESULTS: Compared with the sedentary group, the TCC group had significantly better scores in resting heart rate, three minute step test heart rate, modified sit and reach, total body rotation test on both right and left side (p < 0.01), and both right and left leg standing with eyes closed (p < 0.05). According to the American Fitness Standards, the TCC group attained the 90th percentile rank for sit and reach and total body rotation test, right and left. CONCLUSION: Long term regular TCC exercise has favourable effects on the promotion of balance control, flexibility, and cardiovascular fitness in older adults.

Accidental Falls↗

Senescence-associated (beta)-galactosidase reflects an increase in lysosomal mass during replicative ageing of human endothelial cells.

Senescence-associated (beta)-galactosidase is widely used as a biomarker of replicative senescence. However, it remains unknown whether this is a distinct enzyme active at pH 6, and differentially expressed in senescence, or a manifestation of an increase in the classic acid lysosomal (beta)-galactosidase. Here we have investigated the origin of senescence-associated-(beta)-galactosidase activity by modifying the intracellular and lysosomal pH of young and senescent human umbilical vein endothelial cells and examining the effect of these manipulations on the levels of activity, using a flow cytometric assay. Lysosomal alkalinisation with chloroquine or bafilomycin A(1), as well as equilibration of the intracellular milieu to pH 6 with nigericin, caused a profound (92-99%) inhibition of the total intracellular (beta)-galactosidase activity. However, independent of pH alterations, senescent cells showed levels of (beta)-galactosidase activity three- to sixfold higher than young cells. This increase in activity occurred in parallel to an increase in (beta)-galactosidase protein levels. Acridine Orange staining revealed an increase in lysosomal content with replicative age, which correlated with the increase in (beta)-galactosidase. These findings demonstrate that senescence-associated (beta)-galactosidase is a manifestation of residual lysosomal activity at a suboptimal pH, which becomes detectable due to the increased lysosomal content in senescent cells.

Acridine Orange↗

Genetic and environmental influences on body fat distribution, fasting insulin levels and CVD: are the influences shared?

Central body fat distribution has been shown to be related to hyperinsulinemia, insulin resistance, hypertriglyceridemia, and atherosclerosis to a greater degree than general obesity. There are known to be both genetic and environmental effects on all components of this clustering. Whether these genetic effects are due to one set of genes in common to the components or whether genetic influences on insulin resistance and/or general/abdominal fatness 'turn on' other genes that affect other components of the syndrome is not clear. We analyzed data from the Swedish Adoption/Twin Study of Aging (60% female; monozygotic = 116, dizygotic = 202; average age 65 years) to determine whether there were genetic and/or environmental factors shared among general body fat distribution, abdominal body fat distribution, fasting insulin levels and cardiovascular disease. We found additive genetic effects in males to be significantly different from those in females with genetic effects accounting for variance in waist-hip ratio (males = 28%; females = 49%), body mass index (males = 58%; females = 73%), fasting insulin levels (FI) (males = 27%; females = 49%), and cardiovascular disease (CVD) (males = 18%; females = 37%). There were also shared genetic and environmental effects among all the variables except CVD, but a majority of the genetic variance for these measures was trait specific.

Abdomen↗

Effects of cyclophosphamide on protein expression of rat embryo at end of pre-gastrulation stage in vivo.

AIM: To seek a sensitive time point for pre-gastrulation embryos exposed to developmental toxic agents, and to establish a molecular biomarker to evaluate the mechanism of cyclophosphamide-induced embryonic abnormalities in vivo. METHODS: Pregnant rats on d 3 of gestation were given i.p. cyclophosphamide (Cyc) 10, 20, 40 mg.kg-1. SDS-PAGE was performed to qualitatively observe the target proteins in d 8 rat embryos. RESULTS: The expression of the protein with a molecular weight (M(r)) of approximately 70 kDa distinctively increased and that of the blastocyst-specific protein (M(r) 14.4 kDa) disappeared in Cyc 40 mg.kg-1 group. CONCLUSION: Day 8 of rat gestation could be an optimum time point for understanding developmental toxicity of mammalian embryo during pregastrulation, and the expression of the proteins with M(r) 70 kDa and 14.4 kDa at this point could be employed as a molecular biomarker to demonstrate embryoteratology objectively and sensitively.

Abnormalities, Drug-Induced↗

[Changes of endometrial macrophages and nature kill cells during luteal phase and early pregnancy].

OBJECTIVE: To investigate the effect of endometrial microenvironment on pregnancy. METHODS: The number of macrophage and nature kill (NK) cells in decidua and endometrium were determined in 19 cases of early pregnancy and 11 non-pregnant women respectively by cytometric analysis. RESULTS: The percentages of macrophages (leukocyte antigen molecules CD14 positive) and NK cells (CD56 positive) were significantly increased in decidua of first trimester as compared with those in luteal endometrium (P < 0.01). The number of CD(56)(+)CD(16)(-) subset of NK cells increased significantly during early pregnancy. While the number of CD(56)(+)CD(16)(+) subset did not change. CONCLUSION: The endometrial macrophages and NK cells may be involved in the mechanism of the fetal protective immune reaction during pregnancy.

Adult↗

Mechanism of UV light-induced photorelaxation in isolated rat aorta.

Isolated rat thoracic aorta which is pharmacologically precontracted by phenylephrine induces photorelaxation when exposed to long wave length UV-light. The aim of the present study was to characterize the mechanism of UV-light induced by photorelaxation in the rat aorta. 1. UV light relaxed both endothelium-intact and -denuded rat aortic rings contracted by phenylephrine. The magnitude of relaxation on UV light was dependent on the exposure time and slightly greatly in endothelium-denuded rings than in endothelium-intact preparations. 2. L-NAME (10 nM-100 uM) but not D-NAME completely inhibited the photorelaxation in a concentration dependent manner. 3. The UV-induced relaxation was inhibited by methylene blue (1 -100 uM), and verapamil (100 nM), and removal of extracellular Ca2+. In contrast, UV-light induced photorelaxation was potentiated by N(w)-nitro-Larginine (L-NOARG) treatment. 4. In immunocytochemical analysis of UV-light induced iNOS and eNOS expression in rat aortas, at which expression levels were increased in a time-dependent manner on UV-irradiation in aortic endothelium and smooth muscle, respectively. These results suggest that UV light-induced photorelaxation may be due to nitric oxide from exogenously administered L-arginine as well as endogenous nitric oxide donors such as amino acid and arginine derivatives. Additional suggestion is that UV light stimulates the expression of nitric oxide synthases, and its activity for nitric oxide generation is dependent on cytosolic Ca2+ originated from extracellular space.

Acetylcholine↗

Pig-n, a mammalian homologue of yeast Mcd4p, is involved in transferring phosphoethanolamine to the first mannose of the glycosylphosphatidylinositol.

Many cell surface proteins are anchored to the membrane via a glycosylphosphatidylinositol (GPI) moiety, which is attached to the C terminus of the proteins. The core of the GPI anchor is conserved in all eukaryotes but is modified by various side chains. We cloned a mouse phosphatidylinositol glycan-class N (Pig-n) gene that encodes a 931amino acid protein expressed in the endoplasmic reticulum, which is homologous to yeast Mcd4p. We disrupted the gene in F9 embryonal carcinoma cells. In the Pig-n knockout cells, the first mannose in the GPI precursors was not modified by phosphoethanolamine. Nevertheless, further biosynthetic steps continued with the addition of the third mannose and the terminal phosphoethanolamine. The surface expression of Thy-1 was only partially affected, indicating that modification of the first mannose by phosphoethanolamine is not essential for attachment of GPI anchors in mammalian cells. An inhibitor of GPI biosynthesis, YW3548/BE49385A, inhibited transfer of phosphoethanolamine to the first mannose in mammalian cells but only slightly affected the surface expression of GPI-anchored proteins. Biosynthesis of GPI in the Pig-n knockout cells was not affected by YW3548/BE49385A, and yeast overexpressing MCD4 was highly resistant to YW3548/BE49385A, suggesting that Pig-n and Mcd4p are targets of this drug.

Animals↗

GPI1 stabilizes an enzyme essential in the first step of glycosylphosphatidylinositol biosynthesis.

Attachment of glycosylphosphatidylinositol (GPI) is essential for the surface expression of many proteins. Biosynthesis of glycosylphosphatidylinositol is initiated by the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol. In mammalian cells, this reaction is mediated by a complex of PIG-A, PIG-H, PIG-C, and GPI1. This complexity may be relevant for regulation and for usage of a particular phosphatidylinositol. However, the functions of the respective components have been unclear. Here we cloned the mouse GPI1 gene and disrupted it in F9 embryonal carcinoma cells. Disruption of the GPI1 gene caused a severe but not complete defect in the generation of glycosylphosphatidylinositol-anchored proteins, indicating some residual biosynthetic activity. A complex of PIG-A, PIG-H, and PIG-C decreased to a nearly undetectable level, whereas a complex of PIG-A and PIG-H was easily detected. A lack of GPI1 also caused partial decreases of PIG-C and PIG-H. Therefore, GPI1 stabilizes the enzyme by tying up PIG-C with a complex of PIG-A and PIG-H.

Animals↗

Multiple mitochondrial viruses in an isolate of the Dutch Elm disease fungus Ophiostoma novo-ulmi.

The nucleotide sequences of three mitochondrial virus double-stranded (ds) RNAs, RNA-4 (2599 nucleotides), RNA-5 (2474 nucleotides), and RNA-6 (2343 nucleotides), in a diseased isolate Log1/3-8d2 (Ld) of the Dutch elm disease fungus Ophiostoma novo-ulmi have been determined. All these RNAs are A-U-rich (71-73% A + U residues). Using the fungal mitochondrial genetic code in which UGA codes for tryptophan, the positive-strand of each of RNAs 4, 5, and 6 contains a single open reading frame (ORF) with the potential to encode a protein of 783, 729, and 695 amino acids, respectively, all of which contain conserved motifs characteristic of RNA-dependent RNA polymerases (RdRps). Sequence comparisons showed that these RNAs are related to each other and to a previously characterized RNA, RNA-3a, from the same O. novo-ulmi isolate, especially within the RdRp-like motifs. However, the overall RNA nucleotide and RdRp amino acid sequence identities were relatively low (43-55% and 20-32%, respectively). The 5'- and 3'-terminal sequences of these RNAs are different, but they can all be folded into potentially stable stem-loop structures. Those of RNA-4 and RNA-6 have inverted complementarity, potentially forming panhandle structures. Their molecular and biological properties indicate that RNAs 3a, 4, 5, and 6 are the genomes of four different viruses, which replicate independently in the same cell. These four viruses are also related to a mitochondrial RNA virus from another fungus, Cryphonectria parasitica, recently designated the type species of the Mitovirus genus of the Narnaviridae family, and to a virus from the fungus Rhizoctonia solani. It is proposed that the four O. novo-ulmi mitochondrial viruses are assigned to the Mitovirus genus and designated O. novo-ulmi mitovirus (OnuMV) 3a-Ld, 4-Ld, 5-Ld, and 6-Ld, respectively. Northern blot analysis indicated that O. novo-ulmi Ld nucleic acid extracts contain more single-stranded (ss, positive-stranded) RNA than dsRNA for all three newly described mitoviruses. O. novo-ulmi RNA-7, previously believed to be a satellite-like RNA, is shown to be a defective RNA, derived from OnuMV4-Ld RNA by multiple internal deletions. OnuMV4-Ld is therefore the helper virus for the replication of both RNA-7 and another defective RNA, RNA-10. Sequence comparisons indicate that RNA-10 could be derived from RNA-7, as previously suggested, or derived directly from RNA-4.

3' Untranslated Regions↗

Regulation of protein phosphatase 2A activity by heat shock transcription factor 2.

Heat shock transcription factor (HSF) mediates the stress-induced expression of heat shock protein genes (hsp). However, HSF is required for normal cell function even in the absence of stress and is important for cell cycle progression, but the mechanism that mediates these effects of HSF is unknown. Here, it is shown that a member of the HSF family, HSF2, interacts with the PR65 (A) subunit of protein phosphatase 2A (PP2A). HSF2 binding to PR65 blocks its interaction with the catalytic subunit, due to competition between HSF2 and catalytic subunit for the same binding site in PR65. In addition, overexpression of HSF2 stimulates PP2A activity in cells, indicating the relevance of HSF2 as a regulator of PP2A in vivo. These results identify HSF2 as a dual function protein, capable of regulating both hsp expression and PP2A activity. This could function as a mechanism by which hsp expression is integrated with the control of cell division or other PP2A-regulated pathways.

Animals↗

Expression of a functional N-methyl-D-aspartate-type glutamate receptor by bone marrow megakaryocytes.

Better understanding of hemostasis will be possible by the identification of new lineage-specific stimuli that regulate platelet formation. We describe a novel functional megakaryocyte receptor that belongs to a family of ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype responsible for synaptic neurotransmission in the central nervous system (CNS). Northern blotting and reverse-transcriptase polymerase chain reaction (RT-PCR) studies identified expression of NMDAR1 and NMDAR2D type subunit mRNA in rat marrow, human megakaryocytes, and MEG-01 clonal megakaryoblastic cells. Immunohistochemistry and in vivo autoradiographic binding of the NMDA receptor-specific antagonist MK-801 confirmed that megakaryocytes expressed open channel-forming NMDA receptors in vivo. Western blots indicated that megakaryocyte NMDAR1 was either unglycosylated or only glycosylated to low levels, and of identical size to CNS-type NMDAR1 after deglycosylation with endoglycosidase F/peptide-N-glycosidase F. In functional studies, we demonstrated that NMDA receptor activity was necessary for phorbol myristate acetate (PMA)-induced differentiation of megakaryoblastic cells; NMDA receptor blockade by specific antagonists significantly inhibited PMA-mediated increases in cell size, CD41 expression, and adhesion of MEG-01 cells. These results provide evidence for a novel pathway by which megakaryocytopoiesis and platelet production may be regulated.

Animals↗