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Biomedical subjects

Jun Lu

Publications and source records attributed to Jun Lu.

At least 91 records · Page 5Linked to original sources
PubMed2005

Systematic discovery of regulatory motifs in human promoters and 3' UTRs by comparison of several mammals.

Comprehensive identification of all functional elements encoded in the human genome is a fundamental need in biomedical research. Here, we present a comparative analysis of the human, mouse, rat and dog genomes to create a systematic catalogue of common regulatory motifs in promoters and 3' untranslated regions (3' UTRs). The promoter analysis yields 174 candidate motifs, including most previously known transcription-factor binding sites and 105 new motifs. The 3'-UTR analysis yields 106 motifs likely to be involved in post-transcriptional regulation. Nearly one-half are associated with microRNAs (miRNAs), leading to the discovery of many new miRNA genes and their likely target genes. Our results suggest that previous estimates of the number of human miRNA genes were low, and that miRNAs regulate at least 20% of human genes. The overall results provide a systematic view of gene regulation in the human, which will be refined as additional mammalian genomes become available.

3' Untranslated Regions↗
PubMed2005

Histone acetyltransferase activity of p300 enhances the activation of IL-18 promoter.

Interleukin-18 (IL-18), an important regulator of innate and acquired immune responses expressed from a variety of cell types, is a pleiotropic cytokine in the development of T helper type 1 (Thl) cells. The p300/CBP (CREB-binding protein) coactivator proteins are important histone acetyltransferases (HATs) that regulate the transcription of many genes. Whether p300/CBP play a role in the IL-18 expression has not been investigated previously. In this study, we analyzed the roles of p300 in the regulation of mouse IL-18 by using RT-PCR and a series of co-transfection studies. We showed that p300 had a stimulating effect on the endogenous IL-18 mRNA synthesis and on the activity of IL-18 p1 promoter. The results also showed that IL-18 p1 promoter activity was enhanced by p300 in a dose-dependent manner. Moreover, the p300-mediated activation function can be suppressed by the adenovirus E1A protein, which inhibits the HAT function of p300. Also, a mutation in p300 HAT region abolished the effect of p300 on IL-18 activation. These data further indicate that the acetylase activity of p300 was indispensable to its function. Furthermore, we found that p300 was able to enhance the effect of the transcription factor c-Fos on activation of the IL-18 promoter. Data presented in this paper implicate important roles of p300 in the transcriptional regulation of IL-18.

Acetyltransferases↗
PubMed2005

Effects of ischaemia-mimetic factors on isolated rat ventricular myocytes.

Conventional ischaemia-mimetic solutions contain several key components for inducing hypoxia, glucose deficiency, acidosis, lactate accumulation and hyperosmosis. The effect of each component on myocyte contractility during cardiac ischaemia was investigated in this study. A video-based edge-detection system was used to monitor single ventricular myocytes isolated from the rat. The effect of each factor was compared by preparing the following ischaemia-mimetic solutions: solution A, containing all of the above-mentioned factors; and solutions B, C, D, E and F, each with one of the factors excluded. The solutions that contained lactate severely reduced the contractility of the cardiomyocytes, but cell contraction did not differ significantly between the cardiomyocytes in these solutions. The effect of the solution without the acidosis-inducing component was weaker than that of the conventional ischaemia-mimetic solution. The solution lacking lactate produced the least depression of cell contractility. Lactate impaired cardiomyocyte contractility in a concentration-dependent manner. Our observations suggest that lactate is the main contributor to cardiac ischaemic injury and that its effects are attributable to acidosis and are concentration dependent. Imposition of hypoxia, glucose deficiency and hyperosmosis had little impact on the cardiomyocytes.

Acidosis↗
PubMed2005

Histone acetylation regulates both transcription initiation and elongation of hsp22 gene in Drosophila.

Histone acetylation is associated with transcriptional activation of many genes. However, the role of acetylation in transcriptional regulation of heat shock protein genes (hsp) still remains an obscure issue. Here we examined the effects of histone deacetylase inhibitors (HDIs), trichostatin A, and sodium butyrate, on changes in acetylation level of core histones and on expression of hsp22 gene in Drosophila melanogaster. The results showed that both HDIs elevated the acetylation level of histone H3. By using the chromatin immunoprecipitation, we located the HDI-induced H3 hyperacetylation at both the promoter and the downstream of RNA polymerase II of the transcribing hsp22 gene. Meanwhile, the elevated acetylation level increased the accessibility of heat shock factor to target cis-acting regulatory sites. We conclude that histone acetylation stimulates the transcription initiation and promotes the transcription elongation, thereby up-regulating both basal and inducible expression of hsp22 in D. melanogaster.

Acetylation↗
PubMed2005

Highly enantioselective allylation of aldehydes catalyzed by indium(III)-PYBOX complex.

A chiral indium(III)-PYBOX complex prepared from indium triflate and chiral PYBOX has been discovered to effect high enantioselectivities in the addition of allyltributyl stannane to aldehydes. The allylation of a variety of aromatic, alpha,beta-unsaturated, and aliphatic aldehydes resulted in good yields and high enantioselectivities (up to 94% ee).

Aldehydes↗
PubMed2005

The antituberculosis, antitumor, multibranched dodecafuranoarabinan of Mycobacterium species has been assembled from a single n-pentenylfuranoside source.

An n-pentenyl furanosyl-1,2-orthoester can function as a donor or be rearranged leading to an n-pentenyl furanoside acceptor which is glycosylated by its progenitor, regioselectively or doubly, thereby enabling rapid fabrication of a multibranched dodecasaccharide, known to possess a wide variety of biological interactions.

Antineoplastic Agents↗
PubMed2005

Modified madigan prostatectomy: a procedure preserved prostatic urethra intact.

A total of 92 patients with benign prostatic hyperplasia (BPH) were subjected to modified Madigan prostatectomy (MPC) for a much satisfactory effect in open prostatectomy surgery. Exposing anterior prostatic urethra near the bladder neck and conjunct cystotomy modified the MPC procedure. This modified procedure preserved prostatic urethra intact and could also deal with intracystic lesions at the same time. The intact of prostatic urethra was kept completely or largely in 86 cases. The amount of blood loss during modified procedure was less. The mean operative time was 105 min. Seventy patients had been followed up for 3-24 months. The postoperative average Qmax was 19. 2 ml/s. The cystourethrography revealed that the urethra and bladder neck were intact in 10 patients postoperatively. Furthermore, the prostatic urethra was obviously wider after modified MPC. The modified MPC can reduce the occurrence of urethra injury and enlarge the MPC indications. The modified technique is easy to perform with less complications and much satisfactory clinical result.

Follow-Up Studies↗
PubMed2005

Leupeptin-sensitive proteases involved in cell survival after X-ray irradiation in human RSa cells.

Proteases have received attention as important cellular components responsible for stress response in human cells. However, little is known about the role of proteases in the early steps of cell response after X-ray irradiation. In the present study, we first searched for proteases whose activity levels are changed soon after X-ray irradiation in human RSa cells with a high sensitivity to X-ray cell-killing. RSa cells showed an increased level of fibrinolytic protease activity within 10 min after irradiation with X-ray (up to 3 Gy). The induced protease activity was proved to be inhibited by leupeptin. We next examined whether this protease inducibility is related to the X-ray susceptibility of cells. Treatment of RSa cells with leupeptin prior to X-ray irradiation resulted in lowered colony survival and an increased ratio of G(2)/M-arrested cells and apoptotic cells. These results suggest that leupeptin-sensitive proteases are involved in the resistance of human RSa cells to X-ray cell-killing.

Apoptosis↗
PubMed2005

The hypothalamic integrator for circadian rhythms.

Although the suprachiasmatic nucleus (SCN) is well established as providing a genetically based clock for timing circadian rhythms, the mechanisms by which the timing signal is translated into circadian rhythms of behavior and underlying physiology have only recently come to light. The bulk of the SCN outflow terminates in a column of tissue that arches upward and backward from the SCN, and which includes the subparaventricular zone (SPZ) and the dorsomedial nucleus of the hypothalamus. Neurons within the dorsal SPZ are necessary for organizing circadian rhythms of body temperature, whereas neurons in the ventral SPZ are needed for circadian rhythms of sleep and waking. Ventral SPZ neurons in turn relay to the dorsomedial nucleus, which is crucial for producing circadian rhythms of sleep and waking, locomotor activity, feeding and corticosteroid production. This multistage processor provides the animal with flexibility so that environmental cues, such as food availability, ambient temperature and social interactions, can be integrated with the clock signal to sculpt an adaptive pattern of rhythmic daily activities that maximize the chances of survival and reproduction.

Animals↗
PubMed2005

Fabrication of high-aspect-ratio Prussian blue nanotubes using a porous alumina template.

Prussian blue nanotubes were fabricated by using a sequential deposition technique inside the 60-nm well-ordered pores of anodic alumina. By varying the deposition parameters and the dimensions of the template, we could tailor the length and the outer as well as the inner diameter of the tubes. The nanotubes were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD).

Aluminum Oxide↗
PubMed2005

A minimal domain responsible for Munc13 activity.

Munc13 proteins are essential in neurotransmitter release, controlling the priming of synaptic vesicles to a release-ready state. The sequences responsible for this priming activity are unknown. Here we identify a large alpha-helical domain of mammalian Munc13-1 that is autonomously folded and is sufficient to rescue the total arrest in neurotransmitter release observed in hippocampal neurons lacking Munc13s.

Animals↗
PubMed2005

Increased expression of GRP94 protein is associated with decreased sensitivity to X-rays in cervical cancer cell lines.

PURPOSE: Radiation therapy is one of the standard treatments for cervical cancer. Glucose regulated protein 94 (GRP94) is a molecular chaperone, which increases in amount after X-ray irradiation. This study examined the involvement of GRP94 in radio-resistance in human cervical cancer cells. MATERIALS AND METHODS: Seven human cervical carcinoma cell lines (HeLa, SKG-I, SKG-IIIb, QG-U, Caski, SiHa and C33A) were examined for basal levels of GRP94 protein by western blotting analysis. Sensitivity to X-ray irradiation of these cell lines was determined with a colony survival assay. The suppression of GRP94 expression was performed using specific small-interfering RNA (siRNA) in HeLa and Caski cells. RESULTS: HeLa cells and QG-U cells, with higher basal levels of GRP94, exhibited a low sensitivity to X-ray cell killing. In HeLa cells, the sensitivity increased when protein GRP94 levels were reduced by specific siRNA transfection. However, a reduction in GRP94 protein had little effect on the X-ray sensitivity of Caski cells, which expressed low basal GRP94 protein levels but showed a low sensitivity to X-rays. CONCLUSIONS: High basal protein levels of GRP94 were correlated with a modest decrease in sensitivity to X-ray cell death in some cervical cancer cell lines. These results suggest that higher GRP94 protein expression is one of the molecular mechanisms causing resistance to radiation, and therefore GRP94 siRNA might be useful in tumor-specific gene therapy by reversing radio-resistance prior to radiation in cervical cancer.

Biomarkers, Tumor↗
PubMed2005

Function of c-Fos-like and c-Jun-like proteins on trichostatin A-induced G2/M arrest in Physarum polycephalum.

The homologs of transcription factors c-Fos and c-Jun have been detected in slime mold Physarum polycephalum during progression of the synchronous cell cycle. Here we demonstrated that c-Fos-like and c-Jun-like proteins participated in G2/M transition by the regulation of the level of Cyclin B1 protein in P. polycephalum. The study of antibody neutralization revealed that interruption of the functions of c-Fos-like and c-Jun-like proteins resulted in G2/M transition arrest, implicating their functional roles in cell cycle control. When G2/M transition was blocked by histone deacetylase inhibitor trichostatin A, changes in c-Fos- and c-Jun-like protein levels, and hyperacetylation of c-Jun-like protein, were observed. The data suggest that in P. polycephalum, c-Fos- and c-Jun-like proteins may be the key factors in the regulation of histone acetylation-related G2/M transition, involving the coordinated expression and hyperacetylation of these proteins.

Animals↗
PubMed2005

Mutations in the C-terminal region of TraM provide evidence for in vivo TraM-TraD interactions during F-plasmid conjugation.

Conjugation is a major mechanism for disseminating genetic information in bacterial populations, but the signal that triggers it is poorly understood in gram-negative bacteria. F-plasmid-mediated conjugation requires TraM, a homotetramer, which binds cooperatively to three binding sites within the origin of transfer. Using in vitro assays, TraM has previously been shown to interact with the coupling protein TraD. Here we present evidence that F conjugation also requires TraM-TraD interactions in vivo. A three-plasmid system was used to select mutations in TraM that are defective for F conjugation but competent for tetramerization and cooperative DNA binding to the traM promoter region. One mutation, K99E, was particularly defective in conjugation and was further characterized by affinity chromatography and coimmunoprecipitation assays that suggested it was defective in interacting with TraD. A C-terminal deletion (S79*, where the asterisk represents a stop codon) and a missense mutation (F121S), which affects tetramerization, also reduced the affinity of TraM for TraD. We propose that the C-terminal region of TraM interacts with TraD, whereas its N-terminal domain is involved in DNA binding. This arrangement of functional domains could in part allow TraM to receive the mating signal generated by donor-recipient contact and transfer it to the relaxosome, thereby triggering DNA transfer.

Amino Acid Substitution↗
PubMed2005

Lifespan extension and elevated hsp gene expression in Drosophila caused by histone deacetylase inhibitors.

The heat shock proteins (Hsps) play a positive role in lifespan determination, and histone acetylation has been shown to be involved in transcription of hsp genes in Drosophila. To further determine if hsp22 and hsp70 expression is correlated with lifespan, and if histone acetylation participates in this process, RNA levels for hsp22 and hsp70 were analyzed throughout the lifespan in the long-lived and short-lived iso-female lines. The results showed that hsp22 and hsp70 RNA levels were higher in long-lived line than in short-lived line and that the long-lived flies responded more rapidly to heat but were more tolerant to high temperature. Moreover, we investigated the influences of histone acetylation modification on longevity and on hsp gene expression by using histone deacetylase (HDAC) inhibitors TSA and BuA. The results demonstrated that both inhibitors were able to extend the lifespan and promote hsp22 and hsp70 expression. However, the optimal concentrations of these inhibitors, and probably the mechanisms of their actions, vary with the genetic background. In addition, we showed that HDAC inhibitors caused the hyperacetylation of core histone H3, implicating the involvement of chromatin modulation in hsp gene transcription. These data suggested a close correlation among histone acetylation, hsp gene expression and longevity in D. melanogaster.

Animals↗
PubMed2005

Water and heat transport in hilly red soil of southern China: I. Experiment and analysis.

Studies on coupled transfer of soil moisture and heat have been widely carried out for decades. However, little work has been done on red soils, widespread in southern China. The simultaneous transfer of soil moisture and heat depended on soil physical properties and the climate conditions. Red soil is heavy clay and high content of free iron and aluminum oxide. The climate conditions are characterized by the clear four seasons and the serious seasonal drought. The great air temperature differences annually and diurnally result in significant fluctuation in soil temperature in top layer. The closed and evaporating columns experiments with red soil were conducted to simulate the coupled transfer of soil water and heat under the overlaying and opening fields' conditions, and to analyze the effects of soil temperature gradient on the water transfer and the effects of initial soil water contents on the transfer of soil water and heat. The closed and evaporating columns were designed similarly with about 18 degrees C temperatures differences between the top and bottom boundary, except of the upper end closed or exposed to the air, respectively. Results showed that in the closed column, water moved towards the cold end driven by temperature gradient, while the transported water decreased with the increasing initial soil water content until the initial soil water content reached to field capacity equivalent, when almost no changes for the soil moisture profile. In the evaporating column, the net transport of soil water was simultaneously driven by evaporation and temperature gradients, and the drier soil was more influenced by temperature gradient than by evaporation. In drier soil, it took a longer time for the temperature to reach equilibrium, because of more net amount of transported water.

Journal Article↗
PubMed2005

Water and heat transport in hilly red soil of southern China: II. Modeling and simulation.

Simulation models of heat and water transport have not been rigorously tested for the red soils of southern China. Based on the theory of nonisothermal water-heat coupled transfer, a simulation model, programmed in Visual Basic 6.0, was developed to predict the coupled transfer of water and heat in hilly red soil. A series of soil column experiments for soil water and heat transfer, including soil columns with closed and evaporating top end, were used to test the simulation model. Results showed that in the closed columns, the temporal and spatial distribution of moisture and heat could be very well predicted by the model, while in the evaporating columns, the simulated soil water contents were somewhat different from the observed ones. In the heat flow equation from Taylor and Lary (1964), the effects of soil water evaporation on the heat flow is not involved, which may be the main reason for the differences between simulated and observed results. The predicted temperatures were not in agreement with the observed one with thermal conductivities calculated by de Vries and Wierenga equations, so that it is suggested that K(h), soil heat conductivity, be multiplied by 8.0 for the first 6.5 h and by 1.2 later on. Sensitivity analysis of soil water and heat coefficients showed that the saturated hydraulic conductivity, K(S), and the water diffusivity, D(theta), had great effects on soil water transport; the variation of soil porosity led to the difference of soil thermal properties, and accordingly changed temperature redistribution, which would affect water redistribution.

Journal Article↗