Definitive structural identities of Pneumocystis jirovecii sterols.
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Cholesterol↗
Biomedical subjects
Hui Zhao
Publications and source records attributed to Hui Zhao.
Replication checkpoint protein Mrc1 is regulated by Rad3 and Tel1 in fission yeast.
Fission yeast Mrc1 (mediator of replication checkpoint 1) is an adaptor checkpoint protein required for Rad3-dependent activation of the checkpoint kinase Cds1 in response to arrest of replication forks. Here we report studies on the regulation of Mrc1 by phosphorylation. Replication arrest induced by hydroxyurea (HU) induces Mrc1 phosphorylation that is detected by a change in Mrc1 electrophoretic mobility. Phosphorylation is maintained in cds1Delta, rad3Delta, and tel1Delta single mutants but eliminated in a rad3Delta tel1Delta double mutant. Mrc1 has two clusters of S/TQ motifs that are potential Rad3/Tel1 phosphorylation sites. Mutation of six S/TQ motifs in these two clusters strongly impairs Mrc1 phosphorylation. Two motifs located at S604 and T645 are vital for HU resistance. The T645A mutation strongly impairs a Cds1-Mrc1 yeast two-hybrid interaction that is dependent on a functional forkhead-associated (FHA) domain in Cds1, indicating that phosphorylation of T645 mediates Mrc1's association with Cds1. Consistent with this model, the T645 region of Mrc1 effectively substitutes for the T11 region of Cds1 that is thought to be phosphorylated by Rad3 and to mediate FHA-dependent oligomerization of Cds1. The S/TQ cluster that includes S604 is needed for Mrc1's increased association with chromatin in replication-arrested cells. These data indicate that Rad3 and Tel1 regulate Mrc1 through differential phosphorylation to control Cds1.
Base Sequence↗
New approaches to genetic manipulation of mice: tissue-specific expression of ACE.
The renin-angiotensin system (RAS) plays a central role in body physiology, controlling blood pressure and blood electrolyte composition. ACE.1 (null) mice are null for all expression of angiotensin-converting enzyme (ACE). These mice have low blood pressure, the inability to concentrate urine, and a maldevelopment of the kidney. In contrast, ACE.2 (tissue null) mice produce one-third normal plasma ACE but no tissue ACE. They also have low blood pressure and cannot concentrate urine, but they have normal indices of renal function. These mice, while very informative, show that the null approach to creating knockout mice has intrinsic limitations given the many different physiological systems that no longer operate in an animal without a functioning RAS. To investigate the fine control of body physiology by the RAS, we developed a novel promoter swapping approach to generate a more selective tissue knockout of ACE expression. We used this to create ACE.3 (liver ACE) mice that selectively express ACE in the liver but lack all ACE within the vasculature. Evaluation of these mice shows that endothelial expression of ACE is not required for blood pressure control or normal renal function. Targeted homologous recombination has the power to create new strains of mice expressing the RAS in selected subsets of tissues. Not only will these new genetic models be useful for studying blood pressure regulation but also they show great promise for the investigation of the function of the RAS in complicated disease models.
Animals↗
Mice lacking endothelial ACE: normal blood pressure with elevated angiotensin II.
Recently, the concept of local renin-angiotensin systems (RAS) capable of generating angiotensin II apart from the circulation has received considerable attention. To investigate this, we generated ACE 1/3 mice in which one allele of ACE is null and the second allele was engineered to express ACE on the surface of hepatocytes. ACE 1/3 mice express no endothelial ACE and lack ACE within the lungs. Their kidneys contain <7.8% the enzyme levels present in control mice. Plasma conversion of angiotensin I to angiotensin II was 43.3% normal. The baseline blood pressure and renal function of the ACE 1/3 mice were normal, probably as a function of a marked increase of both plasma angiotensin I and angiotensin II. When exposed to 2 weeks of a salt-free diet (a stress diet stimulating the RAS), blood pressure in ACE 1/3 mice decreased to 92.3+/-2.0 mm Hg, a level significantly lower than that of wild-type control mice. The ACE 1/3 mice demonstrate the plasticity of the RAS and show that significant compensation is required to maintain normal, basal blood pressure in a mouse with an impaired local vascular and renal RAS.
Angiotensin I↗
[Changes of 5 alpha-reductase type II activity in sexual gland of diabetic male rats].
OBJECTIVES: To study the changes of sexual gland 5 alpha-reductase type II activity in pubertal and adult rats with diabetes. METHODS: We selected 40 and 90 days old male Wistar rats as pubertal and adult animal model respectively, 30 rats in each group. The rats were randomly divided into three groups: control group (C), diabetic group (D) and diabetes with insulin replacement group (ID). The activity of 5 alpha-reductase type II was measured with thin layer chromatography in the epididymis, prostate and testis. RESULTS: 1. In all sexual glands of pubertal rats, the activity of 5 alpha-reductase type II in D group is significantly lower than that in C and ID groups. 2. In all sexual glands of adult rats. there is no difference in the activity of 5 alpha-reductase type II among these groups. CONCLUSIONS: The activity of 5 alpha-reductase type II is likely to be influenced by metabolic environment, hormonal levels and local specific factors in pubertal rats, but it is relatively stable in adult rats.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
[Lung squamous cell carcinoma-related genes cloned by using suppression subtractive hybridization].
OBJECTIVE: To identify genes differentially expressed in human lung squamous cell carcinoma (LSCC). METHODS: A subtracted cDNA library of human LSCC constructed by using suppression subtracted hybridization (SSH) method was screened. Clones representing mRNAs that were truly differentially expressed in LSCC but not in its adjacent non-cancerous tissues were identified by semi-quantitative RT-PCR in 12 patients with LSCC. Partial novel genes were detected by Northern blot. RESULTS: Ten differentially expressed gene cDNA fragments of LSSC were obtained by SSH. Among them six were known genes; two sequences were identified but their functions were unknown (hypothetical protein); two were novel (GenBank accession numbers AF363068 and AY032661, respectively). The results from semiquantitative RT-PCR showed that the transcription expression level of PPP1CB, calumenin, S100A2, HSNOV1, OCIA and AY032661 was down-regulated in some LSCC cases, while the transcription of HSP90, ferritin, gp96 and AF363068 was up-regulated in others. CONCLUSIONS: Six known genes identified by SSH technique have been implicated in the pathogenesis of lung carcinogenesis, or they are involved in immunological defense mechanism in human body. Two hypothetical proteins probably also play an important role in the pathogenesis of lung cancer. The function of the two novel genes in lung carcinogenesis are under investigation.
Carcinoma, Squamous Cell↗
HBV DNA level and antigen concentration in evaluating liver damage of patients with chronic hepatitis B.
OBJECTIVE: To investigate the correlations between HBV DNA levels and viral antigen concentrations in patients with chronic hepatitis B and their significance in clinical practice. METHODS: The HBV DNA levels and serological markers of 118 patients with chronic hepatitis B and 87 patients with liver cirrhosis who had not been treated with antiviral drugs were determined as well as the other parameters relevant to liver function. RESULTS: The HBV DNA levels of the patients with chronic hepatitis and cirrhosis were expressed as geometric mean+/-SD, 3.83 x 10(6)+/-1.34 copies/ml and 6.98 x 10(5)+/-1.29 copies/ml, and their HBeAg concentrations expressed as the luminescent values rate of sample to control (s/co) were 35.40+/-1.26 and 4.05+/-1.28, respectively. The HBV DNA levels in HBeAg positive group were significantly higher than those in HBeAg negative group (P<0.0001). The correlation coefficient between HBV DNA level and HBeAg or HBsAg concentration was only 0.273 and -0.12. During the recovery of hepatic function, the reduction of ALT or AST in patients with high viral content was significantly lower than that in patients with low viral content. No correlation was observed between HBV DNA and ALT levels. CONCLUSION: There are significant correlations between HBV DNA level and HBeAg concentration, but the coefficient is lower. HBV DNA level is not significantly related to ALT, but it could affect the recovery of liver function.
Adolescent↗
Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints.
Checkpoint kinase (Chk)1 is an evolutionarily conserved protein kinase that was first identified in fission yeast as an essential component of the DNA damage checkpoint. In mice, Chk1 provides an essential function in the absence of environmentally imposed genotoxic stress. Here we show that human cells lacking Chk1 exhibit defects in both the ionizing radiation (IR)-induced S and G(2) checkpoints. In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR. The IR-induced S and G(2) checkpoints were partially restored in Chk1-deficient cells when Cdc25A accumulation was interfered with. Finally, Cdc25A was phosphorylated by Chk1 in vitro on similar sites phosphorylated in vivo, including serine-123. These findings indicate that Chk1 directly phosphorylates Cdc25A during an unperturbed cell cycle, and that phosphorylation of Cdc25A by Chk1 is required for cells to delay cell cycle progression in response to double-strand DNA breaks.
Cell Cycle↗
Selection of potential therapeutics based on in vivo spatiotemporal transcription patterns of heme oxygenase-1.
Heme oxygenase (HO), a key catabolic enzyme in the conversion of heme to bilirubin, is an ideal target for reducing bilirubin production and preventing pathological jaundice in newborn infants. Metalloporphyrins (Mps) have been well characterized as competitive inhibitors of HO and have been evaluated as potential chemopreventive agents for neonatal jaundice. However, in addition to reducing HO activity, many Mps have been shown to increase HO-1 transcription, which would likely reduce their potential therapeutic utility. The differential effects of Mps on the transcription of HO-1 were therefore evaluated in living transgenic (Tg) reporter mice. Of the compounds evaluated, we observed that zinc bis-glycol porphyrin (ZnBG), a potent inhibitor of HO enzyme activity, did not alter HO-1 transcription patterns in Tg mice. Whole body images of HO-1 transcription patterns did, however; reveal increases in HO-1 transcription in Tg mice after treatment with other Mps, heme and cadmium chloride (CdCl(2)). Intravenous injections of CdCl(2) resulted in expression patterns that differed in tempo and location from those observed in Tg mice treated with intraperitoneal injections. Spatiotemporal analyses of transcriptional regulation in living animals accelerated the assessment of an adverse effect of Mps by revealing different patterns of HO-1 transcription. Among the known inhibitors of HO enzyme activity that were evaluated in this study, ZnBG did not significantly affect HO-1 transcription and therefore may be well suited for the prevention of neonatal jaundice.
Animals↗
Coherence length of excitons in a semiconductor quantum well.
We report on the first experimental determination of the coherence length of excitons in semiconductors using the combination of spatially resolved photoluminescence with phonon sideband spectroscopy. The coherence length of excitons in ZnSe quantum wells is determined to be 300-400 nm, about 25-30 times the exciton de Broglie wavelength. With increasing exciton kinetic energy, the coherence length decreases slowly. The discrepancy between the coherence lengths measured and calculated by considering only the acoustic-phonon scattering suggests an important influence of static disorder.
Journal Article↗
Simultaneity of foetal heart rate acceleration and foetal trunk movement determined by foetal magnetocardiogram actocardiography.
We describe a new method of actocardiography, foetal magnetocardiogram (fMCG) actocardiography, which is based on the high sensitivity of the fMCG to foetal trunk movements. We demonstrate the efficacy of the method by applying it to assess the simultaneity of onset of foetal heart rate (FHR) acceleration and foetal trunk movement. The analysis was restricted to events for which the onset of FHR accelerations and foetal movements could be determined accurately, i.e. when FHR was stable and near the average quiescent level just prior to the acceleration. We found that FHR accelerations coincided with or preceded foetal movements nearly all the time. This supports the hypothesis of coordinated control of FHR accelerations and foetal movements more strongly than prior studies, based on other techniques. We also found that beat-to-beat FHR variability often decreased at or near the start of FHR accelerations and that this occurrence was an accurate marker of foetal movement onset, even when foetal movement onset lagged FHR accelerations.
Adolescent↗
[Immediate immunological effect of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line].
OBJECTIVE: To understand the protective efficacy of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line among newborns. METHODS: 2 969 newborns in seven townships in Zhengding County, Hebei Province, were vaccinated with 10 microgram x 3 doses of China-made recombinant hepatitis B vaccine expressed by transgenic Chinese hamster ovary cell line according to the 0 - 1 - 6 month schedule from 1 January 1997 to 31 August 1999. The newborns were to be vaccinated with the first dose within 24 hours after they were born. 1906 serum samples were selected in April 2000 to detect the hepatitis B infection markers, including HBsAg, HBsAb and HbcAb by RIA kits. RESULTS: 2 783 of the 2 969 newborns (93.74%) were vaccinated with three doses, 2 833 of them (95.42%) were vaccinated with the first dose within 24 hours after they were born. The anti-HBs positive rate was 98.25% (S/N >/= 2.1) or 94.26% (S/N >/= 10.0), and the geometric mean titer (GMT) value of antibody was 77.64 within the first year after the whole course vaccination. Then the antibody level decreased gradually with the lapse of time. The HBsAb positive rate was 92.31% (S/N >/= 2.1) or 68.96% (S/N >/= 10.0), and GMT value was 22.86 within the third year after vaccination. The HBsAg positive rates remained less than 1%, the HBcAb positive rates and HBV infection rates remained 1% approximately 3% within 3 years after vaccination. CONCLUSION: The protective efficacy of China-made recombinant hepatitis B vaccine is satisfactory.
Animals↗
Nitric oxide induces hyperpolarization by opening ATP-sensitive K(+) channels in guinea pig spiral modiolar artery.
Nitric oxide (NO) hyperpolarizes vascular smooth muscle cells and dilates blood vessels of various beds, but little is known on cochlear vasculatures. Using in vitro preparations of the spiral modiolar artery (SMA), intracellular electrical recording and labeling techniques, we found that the NO donor DPTA-NONOate (10 microM) caused a hyperpolarization of approximately 9 mV in all the cells that had a low resting potential (RP) level near -40 mV. The hyperpolarization amplitude was concentration-dependent, with a 50% effect concentration (EC(50)) of 1 microM. The responses occur in both smooth muscle and endothelial cells, neither of which was blocked by 18beta-glycyrrhetinic acid. The induced hyperpolarization was completely blocked by glipizide, but not by charybdotoxin, apamin, barium, 4-aminopyridine or tetraethylammonium. The hyperpolarizing responses were imitated by pinacidil (EC(50)=30 microM). The pinacidil-induced response was also blocked by glipizide but not by the other K(+) channel blockers mentioned above. Both DPTA-NONOate and pinacidil had little membrane potential effect on cells that had a high RP level near -75 mV. However, when the high RP cells were depolarized to a level beyond -45 mV by barium, both DPTA-NONOate and pinacidil hyperpolarized these cells not differently from those that initially had a low RP. It is concluded that NO hyperpolarizes the SMA primarily by activating K(ATP) channels in both muscle and endothelial cells.
Adenosine Triphosphate↗
Protective effect of Fructus Lycii polysaccharides against time and hyperthermia-induced damage in cultured seminiferous epithelium.
Lycium barbarum L. (Solanaceae) is a Chinese medicinal plant whose fruits (Fructus Lycii) are used by Chinese physicians for treatment of infertility. However, the active ingredients and the mechanism of action underlying Lycium's fertility-facilitating effects remain unknown. Here we report that Fructus Lycii polysaccharides (FLPS) inhibit time- and hyperthermia-induced structural damage in murine seminiferous epithelium, in vitro. Moreover, we found that FLPS delayed apoptosis in this system, both at normothermic and hyperthermic culture conditions. Oxidative stress was reported to be a major cause of structural degradation and apoptosis in hyperthermic testes, and thus the protective effect of FLPS could implicate an antioxidant mechanism of action. To test this hypothesis we assayed the effect of FLPS on ultraviolet light-induced lipid peroxidation, and cytochrome c reduction by free radicals. We found that FLPS is a potent inhibitor of both of these reactions. Together, these results demonstrate the protective effect of FLPS on time- and hyperthermia-induced testicular degeneration in vitro, indicate the potential mechanism of action for this protective effect, and provide a scientific basis for the traditional use of this plant.
Animals↗
XETOR regulates the size of the proneural domain during primary neurogenesis in Xenopus laevis.
The interaction between early proneural genes and lateral inhibition determines the number of primary neurons. The mechanism for regulating the size of the proneural domain, however, has not been clarified. We show here that inhibition of the function of XETOR in Xenopus, a homolog of human oncoprotein ETO/MTG8, leads to a neurogenic phenotype of expanded proneural domain without alteration in the density of primary neurons. This result suggests that XETOR is a prerequisite for regulating the size of the proneural domain. We further show that such a regulation is accomplished by establishing a negative feedback loop between XETOR and proneural genes except Xngnr-1, as well as by antagonism between XETOR and lateral inhibition.
Amino Acid Sequence↗
Electrochemical polishing of 316L stainless steel slotted tube coronary stents.
Surface smoothness is one of the properties determining the performance of stents. Therefore, surface polishing shows its importance in the exploitation and production of stents. The present study explores electrochemical polishing of 316L stainless steel slotted tube coronary stents produced by laser cutting. Acid pickling was also studied as a pre-treatment of electrochemical polishing of the stents to remove the slag (oxides) formed in the production of the stents. Meanwhile, removal of the material was measured as well, caused by both acid pickling and electrochemical polishing processes. It is found that the slag formed on the surface of stents due to the laser cutting production process could be removed by means of acid pickling. Electrochemical polishing results in a smooth stent surface. Meanwhile, both acid pickling and electrochemical polishing applied in the present study have a proper removal of the stent material.
Journal Article↗
Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application.
Basic scientific research has demonstrated that epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA) and transforming growth factor-alpha (TGF-alpha) are induced by acute tympanic membrane (TM) perforation. The expression of these growth factors peaks during the inflammatory phase and then declines, suggesting their involvement in the healing process of the TM. Expression of EGF receptor, bFGF receptor, PDGF receptor and keratinocyte growth factor (KGF) receptor in the TM has also been reported. Identification of these receptors indicates that the target cells in the TM may be stimulated during the process of healing by the corresponding exogenous growth factor in vivo. Some reports from animal studies showed encouraging effects of EGF, bFGF and PDGF-AA in terms of accelerated or enhanced healing of acute and chronic TM perforations without significant adverse effects. Two reports of clinical trials of topical application of EGF or bFGF for TM perforations revealed mixed results. In this article special considerations for future directions of research into growth factors are discussed and related articles on healing of skin wounds and other lesions are reviewed. Further experimental and clinical studies on the mechanism of action of growth factors, timing of application, selection (either singly or in combination), delivery mode, dose and safety aspects, as well as more clinical trials, are warranted, and will pave the way for clinical application.
Animals↗
Identification of human mannose binding lectin (MBL) recognition sites for novel inhibitory antibodies.
Mannose binding lectin (MBL) binding initiates activation of the lectin complement pathway. Recent studies from our laboratory have demonstrated that MBL-dependent complement activation mediates cellular injury following oxidative stress in vivo and in vitro. A panel of novel inhibitory monoclonal antibodies (MAbs) against MBL (e.g., MAb 3F8, 2A9, and hMBL1.2) has been developed that inhibit MBL binding and lectin pathway activation. Here, we further characterized the interactions of these MAbs and their Fab fragments to MBL. Whole MAbs or their Fab fragments bound to MBL with relatively high affinity. Fab fragments of 3F8 were functionally effective in inhibiting MBL-dependent complement activation, however, steric hindrance of MAb 2A9 was essential for inhibition of MBL-dependent complement activation. We identified the hinge region, and residues EDCVLLL within the carbohydrate recognition domain of MBL as the recognition sites for MAb 3F8 and 2A9, respectively. The interaction of MAbs (e.g., 3F8 and 2A9) to MBL was dependent on the conformation of their recognition sites. These findings demonstrate that MBL binding can be inhibited by at least two separate and independent mechanisms.
Amino Acid Sequence↗