Biomedical subjects

S Bao

Publications and source records attributed to S Bao.

At least 19 recordsLinked to original sources

PubMed2001

The Drosophila double-timeS mutation delays the nuclear accumulation of period protein and affects the feedback regulation of period mRNA.

The Drosophila double-time (dbt) gene, which encodes a protein similar to vertebrate epsilon and delta isoforms of casein kinase I, is essential for circadian rhythmicity because it regulates the phosphorylation and stability of period (per) protein. Here, the circadian phenotype of a short-period dbt mutant allele (dbt(S)) was examined. The circadian period of the dbt(S) locomotor activity rhythm varied little when tested at constant temperatures ranging from 20 to 29 degrees C. However, per(L);dbt(S) flies exhibited a lack of temperature compensation like that of the long-period mutant (per(L)) flies. Light-pulse phase-response curves were obtained for wild-type, the short-period (per(S)), and dbt(S) genotypes. For the per(S) and dbt(S) genotypes, phase changes were larger than those for wild-type flies, the transition period from delays to advances was shorter, and the light-insensitive period was shorter. Immunohistochemical analysis of per protein levels demonstrated that per protein accumulates in photoreceptor nuclei later in dbt(S) than in wild-type and per(S) flies, and that it declines to lower levels in nuclei of dbt(S) flies than in nuclei of wild-type flies. Immunoblot analysis of per protein levels demonstrated that total per protein accumulation in dbt(S) heads is neither delayed nor reduced, whereas RNase protection analysis demonstrated that per mRNA accumulates later and declines sooner in dbt(S) heads than in wild-type heads. These results suggest that dbt can regulate the feedback of per protein on its mRNA by delaying the time at which it is translocated to nuclei and altering the level of nuclear PER during the declining phase of the cycle.

Alleles↗

PubMed2001

Molecular adsorption bond lengths at metal oxide surfaces: failure of current theoretical methods.

New experimental structure determinations for molecular adsorbates on NiO(100) reveal much shorter Ni-C and Ni-N bond lengths for adsorbed CO and NH3 as well as NO (2.07, 1.88, 2.07 A) than previously computed theoretical values, with discrepancies up to 0.79 A, highlighting a major weakness of current theoretical descriptions of oxide-molecule bonding. Comparisons with experimentally determined bond lengths of the same species adsorbed atop Ni on metallic Ni(111) show values on the oxide surface that are consistently larger (0.1-0.3 A) than on the metal, indicating somewhat weaker bonding.

Journal Article↗

PubMed2001

Basal forebrain stimulation changes cortical sensitivities to complex sound.

Experience affects how brains respond to sound. Here, we examined how the sensitivity and selectivity of auditory cortical neuronal responses were affected in adult rats by the repeated presentation of a complex sound that was paired with basal forebrain stimulation. The auditory cortical region that was responsive to complex sound was 2-5 five times greater in area in paired-stimulation rats than in naive rats. Magnitudes of neuronal responses evoked by complex sounds were also greatly increased by associative pairing, as were the percentages of neurons that responded selectively to the specific spectrotemporal features that were paired with stimulation. These findings demonstrate that feature selectivity within the auditory cortex can be flexibly altered in adult mammals through appropriate intensive training.

Acoustic Stimulation↗

PubMed2001

Defective gp130-mediated signal transducer and activator of transcription (STAT) signaling results in degenerative joint disease, gastrointestinal ulceration, and failure of uterine implantation.

The receptor subunit gp130 transduces multiple cell type-specific activities of the leukemia inhibitory factor (LIF)/interleukin (IL)-6 family of cytokines through the signal transducer and activator of transcription (STAT) and src homology 2 domain-bearing protein tyrosine phosphatase (SHP)-2/ras/Erk pathways. To define STAT-dependent physiological responses, we generated mice with a COOH-terminal gp130(DeltaSTAT) "knock-in" mutation which deleted all STAT-binding sites. gp130(DeltaSTAT) mice phenocopyed mice deficient for IL-6 (impaired humoral and mucosal immune and hepatic acute phase responses) and LIF (failure of blastocyst implantation). However, unlike mice with null mutations in any of the components in the gp130 signaling pathway, gp130(DeltaSTAT) mice also displayed gastrointestinal ulceration and a severe joint disease with features of chronic synovitis, cartilaginous metaplasia, and degradation of the articular cartilage. Mitogenic hyperresponsiveness of synovial cells to the LIF/IL-6 family of cyto-kines was caused by sustained gp130-mediated SHP-2/ras/Erk activation due to impaired STAT-mediated induction of suppressor of cytokine signaling (SOCS) proteins which normally limits gp130 signaling. Therefore, the joint pathology in gp130(DeltaSTAT) mice is likely to arise from the disturbance of the otherwise balanced activation of the SHP-2/ras/Erk and STAT signaling cascades emanating from gp130.

Animals↗

PubMed2001

Cortical remodelling induced by activity of ventral tegmental dopamine neurons.

Representations of sensory stimuli in the cerebral cortex can undergo progressive remodelling according to the behavioural importance of the stimuli. The cortex receives widespread projections from dopamine neurons in the ventral tegmental area (VTA), which are activated by new stimuli or unpredicted rewards, and are believed to provide a reinforcement signal for such learning-related cortical reorganization. In the primary auditory cortex (AI) dopamine release has been observed during auditory learning that remodels the sound-frequency representations. Furthermore, dopamine modulates long-term potentiation, a putative cellular mechanism underlying plasticity. Here we show that stimulating the VTA together with an auditory stimulus of a particular tone increases the cortical area and selectivity of the neural responses to that sound stimulus in AI. Conversely, the AI representations of nearby sound frequencies are selectively decreased. Strong, sharply tuned responses to the paired tones also emerge in a second cortical area, whereas the same stimuli evoke only poor or non-selective responses in this second cortical field in naive animals. In addition, we found that strong long-range coherence of neuronal discharge emerges between AI and this secondary auditory cortical area.

Acoustic Stimulation↗

PubMed2001

ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses.

Genotoxic stress triggers the activation of checkpoints that delay cell-cycle progression to allow for DNA repair. Studies in fission yeast implicate members of the Rad family of checkpoint proteins, which includes Rad17, Rad1, Rad9 and Hus1, as key early-response elements during the activation of both the DNA damage and replication checkpoints. Here we demonstrate a direct regulatory linkage between the human Rad17 homologue (hRad17) and the checkpoint kinases, ATM and ATR. Treatment of human cells with genotoxic agents induced ATM/ATR-dependent phosphorylation of hRad17 at Ser 635 and Ser 645. Overexpression of a hRad17 mutant (hRad17AA) bearing Ala substitutions at both phosphorylation sites abrogated the DNA-damage-induced G2 checkpoint, and sensitized human fibroblasts to genotoxic stress. In contrast to wild-type hRad17, the hRad17AA mutant showed no ionizing-radiation-inducible association with hRad1, a component of the hRad1-hRad9-hHus1 checkpoint complex. These findings demonstrate that ATR/ATM-dependent phosphorylation of hRad17 is a critical early event during checkpoint signalling in DNA-damaged cells.

Animals↗

PubMed2001

The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast Schizosaccharomyces pombe.

The p21-activated kinase, Shk1, is required for cell viability, establishment and maintenance of cell polarity, and proper mating response in the fission yeast, Schizosaccharomyces pombe. Previous genetic studies suggested that a presumptive protein methyltransferase, Skb1, functions as a positive modulator of Shk1. However, unlike Shk1, Skb1 is not required for viability or mating of S. pombe cells and contributes only modestly to the regulation of cell morphology under normal growth conditions. Here we demonstrate that Skb1 plays a more significant role in regulating cell growth and polarity under conditions of hyperosmotic stress. We provide evidence that the inability of skb1Delta cells to properly maintain cell polarity in hyperosmotic conditions results from inefficient subcellular targeting of F-actin. We show that Skb1 localizes to cell ends, sites of septation, and nuclei of S. pombe cells. Hyperosmotic shock results in substantial delocalization of Skb1 from cell ends and nuclei, as well as stimulation of Skb1 protein methyltransferase activity. Taken together, our results demonstrate a new role for Skb1 as a mediator of hyperosmotic stress response in fission yeast. We show that the protein methyltransferase activity of the human Skb1 homolog, Skb1Hs, is also stimulated by hyperosmotic stress in fission yeast, providing evidence for evolutionary conservation of a role for Skb1-related proteins as mediators of hyperosmotic stress response, as well as mechanisms involved in regulating this novel class of protein methyltransferases.

Carrier Proteins↗

PubMed2001

Pattern of cyanophycin accumulation in nitrogen-fixing and non-nitrogen-fixing cyanobacteria.

The temporal and spatial accumulation of cyanophycin was studied in two unicellular strains of cyanobacteria, the diazotrophic Cyanothece sp. strain ATCC 51142 and the non-diazotrophic Synechocystis sp. strain PCC 6803. Biochemistry and electron microscopy were used to monitor the dynamics of cyanophycin accumulation under nitrogen-sufficient and nitrogen-deficient conditions. In Cyanothece sp. ATCC 51142 grown under 12 h light/12 h dark nitrogen-fixing conditions, cyanophycin was temporally regulated relative to nitrogenase activity and accumulated in granules after nitrogenase activity commenced. Cyanophycin granules reached a maximum after the peak of nitrogenase activity and eventually were utilized completely. Knock-out mutants were constructed in Synechocystis sp. PCC 6803 cphA and cphB genes to analyze the function of these genes and cyanophycin accumulation under nitrogen-deficient growth conditions. The mutants grew under such conditions, but needed to degrade phycobilisomes as a nitrogen reserve. Granules could be seen in some wild-type cells after treatment with chloramphenicol, but were never found in Delta cphA and Delta cphB mutants. These results led to the conclusion that cyanophycin is temporally and spatially regulated in nitrogen-fixing strains such as Cyanothece sp. ATCC 51142 and represents a key nitrogen reserve in these organisms. However, cyanophycin appeared to play a less important role in the non-diazotrophic unicellular strains and phycobilisomes appeared to be the main nitrogen reserve.

Bacterial Proteins↗

PubMed2001

Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1.

The p21-activated kinase, Shk1, is essential for viability, establishment and maintenance of cell polarity, and proper mating response in the fission yeast, Schizosaccharomyces pombe. Here we describe the characterization of a highly conserved, WD repeat protein, Skb15, which negatively regulates Shk1 in fission yeast. A null mutation in the skb15 gene is lethal and results in deregulation of actin polymerization and localization, microtubule biogenesis, and the cytokinetic machinery, as well as a substantial uncoupling of these processes from the cell cycle. Loss of Skb15 function is suppressed by partial loss of Shk1, demonstrating that negative regulation of Shk1 by Skb15 is required for proper execution of cytoskeletal remodeling and cytokinetic functions. A mouse homolog of Skb15 can substitute for its counterpart in fission yeast, demonstrating that Skb15 protein function has been substantially conserved through evolution.

Actins↗

PubMed2001

Persistent and specific influences of early acoustic environments on primary auditory cortex.

This study demonstrates that the adult form of 'tonotopic maps' of sound frequency in the rat primary auditory cortex (A1) arises from parallel developmental processes involving two cortical zones: the progressive differentiation and refinement of selectively tone-responsive receptive fields within an initially broadly-tuned posterior zone, and the progressive loss of tone-evoked, short-latency response over an initially large, very broadly tuned anterior zone. The formation of tonotopic maps in A1 was specifically influenced by a rat pup's early acoustic environments. Exposure to pulsed tones resulted in accelerated emergence and an expansion of A1 representations of those specific tone frequencies, as well as a deteriorated tonotopicity and broader-than-normal receptive fields. Thus, auditory experiences during early postnatal development are important in shaping the functional development of auditory cortical representations of specific acoustic environments.

Acoustic Stimulation↗

PubMed2001

Depletion of CD4(+) T cells aggravates glomerular and interstitial injury in murine adriamycin nephropathy.

BACKGROUND: CD4(+) T cells play an important role in various types of immunologic renal disease, including lupus nephritis, IgA nephropathy, and crescentic glomerulonephritis. CD4(+) T cells are also major infiltrating lymphocytes in chronic tubulointerstitial inflammation associated with nonimmunological renal diseases. We suspected that CD4(+) T cells might contribute to disease progression and loss of renal function in chronic proteinuric renal disease (CPRD). To investigate this possibility, the effect of monoclonal antibody against CD4(+) lymphocytes (anti-CD4) was studied in a murine model (adriamycin nephropathy) of CPRD. METHODS: Adriamycin nephropathy was produced in male BALB/c mice by a single intravenous injection of adriamycin (11 mg/kg). Anti-CD4 was given by intraperitoneal injection following the development of proteinuria at days 5, 6, 7, 21, and 37 after adriamycin. After six weeks, renal function and histology were studied by histomorphometry, immunohistochemistry, and flow cytometry. RESULTS: Flow cytometric analysis showed a marked decrease in the number of CD4(+) T cells in blood and spleen of the antibody-treated animals (N = 7, P < 0.01). Adriamycin plus CD4(+) depletion mice had significantly greater mesangial expansion, glomerular sclerosis, and interstitial expansion than the mice on adriamycin alone. Interstitial infiltration with macrophages and CD8(+) cells was significantly increased in adriamycin plus CD4(+) depletion mice. Creatinine clearance (17.5 +/- 0.54 vs. 29.2 +/- 0.89 microL/min, P < 0.001) was significantly worse in the adriamycin plus CD4(+) depletion mice than in adriamycin alone mice and correlated with histologic change in glomeruli and interstitium. CONCLUSIONS: Depletion of CD4(+) T cells promotes glomerular and interstitial injury in mice with established adriamycin nephropathy. These findings suggest that CD4(+) T cells have a protective role against the progression of adriamycin nephropathy.

Animals↗

PubMed2001

A practical method for ergonomic and usability evaluation of hand tools: a comparison of three random orbital sander configurations.

Tool and equipment purchasing decisions are constantly made by companies and workers, often with little objective information beyond word of mouth and marketing information. This study presents a pilot investigation of random orbital sanders using ergonomic and usability assessment techniques which can easily be applied in any industry. Three subjects performed a sanding task using three different tool configurations: 1) the current model sander, 2) current model with hose-swivel attachment, and 3) the new "ergonomically designed" model. Physical measurements were taken of muscle activity and wrist motion to complement think-aloud testing and a usability questionnaire. No significant differences were found in physical measurements between the three configurations. Participants strongly preferred the current model over the new model, reporting less perceived discomfort and vibration, despite what appeared to be improvements in the new design. Workplace changes intended to reduce the risk of injury sometimes may have no effect after significant capital investment, or in some cases even increase the risk of injury. Practical assessment of new tools or modifications can quickly determine whether the outcome is indeed an improvement. The results of this tool assessment highlight the need for objective information in tool and equipment design decisions.

Adult↗

PubMed2001

Effects of exogenous interleukin-6 during Pseudomonas aeruginosa corneal infection.

Lack of interleukin-6 (IL-6) during Pseudomonas aeruginosa corneal infection leads to more severe disease with changes in neutrophil recruitment. Exogenous IL-6 leads to increased efficiency of neutrophil recruitment and reduced bacterial loads in corneal infection in both IL-6 gene knockout and wild-type mice. This may be mediated by IL-6 increasing the production of corneal macrophage inflammatory protein 2 and intercellular cell adhesion molecule 1. We conclude that effective recruitment of neutrophils into the cornea is dependent on the production of IL-6 and that early augmentation of IL-6 may be protective in corneal infection.

Animals↗

PubMed2001

The presence of functional luteinizing hormone/chorionic gonadotropin receptors in human sperm.

The functional receptors that bind human CG (hCG) and LH have recently been identified in a number of nongonadal human tissues. The current experiments tested the hypothesis that human ejaculated sperm may also contain them. The data revealed that they, indeed, do as determined by the presence of receptor messenger RNA and receptor protein that can bind (125)I-hCG. The receptors were functional, as indicated by an increase in cyclic AMP levels and activation of sperm protein kinase A following treatment with hCG or LH. Treatment with these hormones, on the other hand, had no effect on sperm protein kinase C activity. Now that the functional LH/hCG receptors are found in human sperm, it is important to determine whether hCG treatment could improve the outcome of infertility procedures.

Adult↗

PubMed2001

Relative effectiveness of HZE iron-56 particles for the induction of cytogenetic damage in vivo.

One of the risks of prolonged manned space flight is the exposure of astronauts to radiation from galactic cosmic rays, which contain heavy ions such as (56)Fe. To study the effects of such exposures, experiments were conducted at the Brookhaven National Laboratory by exposing Wistar rats to high-mass, high-Z, high-energy (HZE) particles using the Alternating Gradient Synchrotron (AGS). The biological effectiveness of (56)Fe ions (1000 MeV/nucleon) relative to low-LET gamma rays and high-LET alpha particles for the induction of chromosome damage and micronuclei was determined. The mitotic index and the frequency of chromosome aberrations were evaluated in bone marrow cells, and the frequency of micronuclei was measured in cells isolated from the trachea and the deep lung. A marked delay in the entry of cells into mitosis was induced in the bone marrow cells that decreased as a function of time after the exposure. The frequencies of chromatid aberrations and micronuclei increased as linear functions of dose. The frequency of chromosome aberrations induced by HZE particles was about 3.2 times higher than that observed after exposure to (60)Co gamma rays. The frequency of micronuclei in rat lung fibroblasts, lung epithelial cells, and tracheal epithelial cells increased linearly, with slopes of 7 x 10(-4), 12 x 10(-4), and 11 x 10(-4) micronuclei/binucleated cell cGy(-1), respectively. When genetic damage induced by radiation from (56)Fe ions was compared to that from exposure to (60)Co gamma rays, (56)Fe-ion radiation was between 0.9 and 3.3 times more effective than (60)Co gamma rays. However, the HZE-particle exposures were only 10-20% as effective as radon in producing micronuclei in either deep lung or tracheal epithelial cells. Using microdosimetric techniques, we estimated that 32 cells were hit by delta rays for each cell that was traversed by the primary HZE (56)Fe particle. These calculations and the observed low relative effectiveness of the exposure to HZE particles suggest that at least part of the cytogenetic damage measured was caused by the delta rays. Much of the energy deposited by the primary HZE particles may result in cell killing and may therefore be "wasted" as far as production of detectable micronuclei is concerned. The role of wasted energy in studies of cancer induction may be important in risk estimates for exposure to HZE particles.

Animals↗

PubMed2001

Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes.

Pre-B-cell colony enhancing factor (PBEF) was first isolated from an activated peripheral blood lymphocyte cDNA library and was found to be involved in the maturation of B-cell precursors. It was subsequently identified as one of the genes upregulated by distending the human fetal membranes in vitro. Here we report on the genomic organization of this gene, which is composed of 11 exons and 10 introns, spanning 34.7 kb of genomic DNA. Neither the gene nor the protein has any homology with other cytokines in any currently available database. The use of two promoters (proximal and distal) may result in differential, tissue specific expression of the PBEF transcripts. The 5'-flanking region lacks the classical sequence motif that would place it with the hematopoietic cytokines; however, it has several putative regulatory elements, suggesting that this gene may be chemically and mechanically responsive to inducers of transcription. The three PBEF mRNA transcripts were observed in both normal and infected human fetal membranes but were significantly upregulated (P<0.05) in severe infection. The PBEF protein was immunolocalized, in both normal and infected tissues, to both the normal fetal cells of the amnion and chorion and the maternal decidua of the membranes, and to the invading neutrophils. These stained strongly and were likely to contribute to the increased expression in infection. The amniotic epithelial cell line (WISH cells) has been used as a model to study PBEF gene modulation. Lipopolysaccharide, interleukin (IL)-1beta, tumour necrosis factor (TNF)alpha and IL-6 all significantly increased the expression of PBEF in 4 h of treatment. The addition of dexamethasone to IL-1beta and TNFalpha significantly reduced the response of PBEF to these cytokines. IL-8 treatment failed to alter PBEF gene expression. Thus PBEF is a cytokine expressed in the normal fetal membranes and upregulated when they are infected. It is likely to have a central role in the mechanism of infection-induced preterm birth.

Blotting, Northern↗

PubMed2001

Induction and repair of HZE induced cytogenetic damage.

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.

Alpha Particles↗

PubMed2001

[Study on the energy transfer fluorescence quenching among combination of acridine yellow-PAR determination of trace iron].

An energy transfers technique between 4-(2-Pyridylazo) resorcinol(PAR) and acridine yellow is studied, and optimum experimental conditions of energy transfer is done as well. It is found that in the aqueous solution of sodium lauryl sulfate, NH3.H2O-NH4Cl buffer solution at pH = 9.2, the energy transfers from acridine yellow to iron(II)-PAR complexes. So a new method of fluorometric energy transfers determination of trace iron(II) by acridine yellow--PAR was described. The range of determination of iron is 0-10 micrograms.L-1. The detection limit for iron is 0.06 microgram.L-1. The method has been applied to the determination of iron in water sample and hair with satisfactory results.

Aminoacridines↗