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ABSTRACT IMPACT: This work may provide new targets for vaccine and immunotherapeutic development against MRSA infections. OBJECTIVES/GOALS: Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Patients with SA SSSI have a high 1-year recurrence. We have shown innate memory protects mice against SA SSSI. The goal of this project is to determine epigenetic mechanisms of protective memory against SA SSSI. METHODS/STUDY POPULATION: We have shown macrophages (Mf) afford protective memory against recurrent SA SSSI in mice. Priming by prior infection reduced skin lesion size and MRSA burden, which correlated with increased Mf in abscesses and lymph nodes. Priming potentiated the opsonophagocytic killing of SA by bone-marrow derived Mf (BMDM) in vitro, and their adoptive transfer into naive skin afforded protective efficacy in vivo. Here, we investigated epigenetic mechanisms of anti-SA efficacy in BMDMs. BMDM from naive (uninfected) or primed (SA SSSI) wild-type C57Bl/6 mice were cultured ex vivo. DNA from BMDM groups were isolated and analyzed for methylation changes using reduced representation bisulfite sequencing (RRBS). Pathway analyses of methylation changes were determined with Panther. RESULTS/ANTICIPATED RESULTS: Present findings indicate the protective memory afforded by BMDM was mediated by epigenetic modifications of the DNA. Using RRBS, we profiled differentially methylated regions (DMR) in DNA from naive vs. primed BMDM. Primed BMDM exhibited significantly different DMRs as compared to naive BMDM. Proximity to known genes were mapped using GREAT. Pathway analyses revealed DMRs predominant in genes integral to immune modulation, such as integrin signaling, cytokine/chemokine networks, and growth regulation. For example, SA-primed BMDM were hypermethylated proximate to GIMAP8 versus naive BMDM, suggesting repression of this protein. Gimap family ligands are small GTPase immune-associated proteins expressed in immune cells known to regulate macrophage lysosomal fusion during parasite infection. DISCUSSION/SIGNIFICANCE OF FINDINGS: These findings reveal epigenetic mechanisms of macrophage innate memory against recurrent MRSA infection. Functional testing of these genes in response to SA infection is needed to confirm their protective role. These insights may provide new targets for vaccine and immunotherapeutic development against MRSA.
We conducted a survey of 16,914 patients to determine the point prevalence of healthcare-associated catheter-associated urinary tract infection (HA-CAUTI) and urinary catheter care in public hospitals in Hong Kong. Overall HA-CAUTI prevalence was 0.27%. Compliance was generally good, except for documenting the date of planned removal and securing the catheter properly.
Recent studies suggest that ketamine produces antidepressant actions via stimulation of mammalian target of rapamycin (mTOR), leading to increased levels of synaptic proteins in the prefrontal cortex. Thus, mTOR activation may be related to antidepressant action. However, the mTOR signalling underlying antidepressant drug action has not been well investigated. The aim of the present study was to determine whether alterations in mTOR signalling were observed following treatment with antidepressant drugs, using ketamine as a positive control. Using Western blotting, we measured changes in the mTOR-mediated proteins and synaptic proteins in rat hippocampal cultures. Dendritic outgrowth was determined by neurite assay. Our findings demonstrated that escitalopram, paroxetine and tranylcypromine significantly increased levels of phospho-mTOR and its down-stream regulators (phospho-4E-BP-1 and phospho-p70S6K); fluoxetine, sertraline and imipramine had no effect. All drugs tested increased up-stream regulators (phospho-Akt and phospho-ERK) levels. Increased phospho-mTOR induced by escitalopram, paroxetine or tranylcypromine was significantly blocked in the presence of specific PI3K, MEK or mTOR inhibitors, respectively. All drugs tested also increased hippocampal dendritic outgrowth and synaptic proteins levels. The mTOR inhibitor, rapamycin, significantly blocked these effects on escitalopram, paroxetine and tranylcypromine whereas fluoxetine, sertraline and imipramine effects were not affected. The effects of escitalopram, paroxetine and tranylcypromine paralleled those of ketamine. This study presents novel in vitro evidence indicating that some antidepressant drugs promote dendritic outgrowth and increase synaptic protein levels through mTOR signalling; however, other antidepressant drugs seem to act via a different pathway. mTOR signalling may be a promising target for the development of new antidepressant drugs.
The repeated administration of methamphetamine (MA) to animals in a single-day ‘binge’ dosing regimen produces damage to dopamine and serotonin terminals and psychosis-like behaviours similar to those observed in MA abusers. The present study aimed to examine the effects of MA binge exposure on 5-HT2A receptors, the subtype of serotonin receptors putatively involved in psychosis. ICR male mice were treated with MA (4 × 5 mg/kg) or saline at 2 h intervals. Recognition memory and social behaviours were sequentially evaluated by a novel location recognition test, a novel object recognition test, a social interaction and a nest-building test to confirm the persistent cognitive and behavioural impairments after this dosing regimen. Subsequently, a hallucinogenic 5-HT2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI)-induced head-twitch, molecular and electrophysiological responses were monitored. Finally, the levels of 5-HT2C, 5-HT1A, 5-HT2A and mGlu2 receptors in the medial prefrontal cortex were determined. MA binge exposure produced recognition memory impairment, reduced social behaviours, and increased DOI-induced head-twitch response, c-Fos and Egr-2 expression and field potentials in the medial prefrontal cortex. Furthermore, MA binge exposure increased 5-HT2A and decreased mGlu2 receptor expression in the medial frontal cortex, whereas 5-HT2C and 5-HT1A receptors were unaffected. These data reveal that the increased behavioural, molecular and electrophysiological responses to DOI might be associated with an up-regulation of 5-HT2A receptors in the medial prefrontal cortex after MA binge exposure. Identifying the biochemical alterations that parallel the behavioural changes in a mouse model of MA binge exposure may facilitate targeting therapies for treatment of MA-related psychiatric disorders.
We present a versatile and facile route for highly sensitive detection of
analytes through coupling the enlargement of gold nanoparticles (Au NPs)
with fluorescence decrease. The fluorescence intensity of dye molecules
(e.g., fluorescein or rhodamine B) significantly decreased with the
increasing concentration of reducing agents, such as hydrogen peroxide and
hydroquinone. The sensitivity for the detection of reducing agents was much
higher than other detection methods based on the absorbance measurement of
enlarged gold nanoparticles or quantum dot-enzyme hybridization. We could
successfully detect acetylthiocholine with the detection limit of several nM
orders, using an enzymatic reaction by acetylcholinesterase, a key route for
the detection of toxic organophosphate compounds. The fluorescence
decreasing approach described in this work requires only a simple addition
of fluorescence dye to the reaction solution without any chemical
modification. The strategy of fluorescence decrease coupled with
nanoparticle growth will be applied on the fluorescent substrate to develop
detection templates for highly sensitive optical biosensor.
Quantitative real time PCR is the most sensitive and widely used method for the analysis of gene expression. The choice of one or several reference genes is very important for a normalization process, which should not fluctuate under stress conditions, to reduce error rate and bias during experimental procedure. In the present study, the expression stability of nine reference genes (two actins, two tubulins, two elongation factor 1α, two ubiquitins, and cyclophilin) during abiotic stresses such as cold, salt, and PEG treatments, was evaluated on Deschampsia antarctica plants using geNorm software. Results from various experimental conditions indicated that cyclophilin and elongation factor 1α were the most stable genes in the leaf and the root, respectively. The expression of the other reference genes varied under stress. The relative quantification of the TACR7 gene varied according to the kind and the number of reference genes used, suggesting the importance of considering the implications of a combination of reference genes under different stress conditions and in different tissues.
McCoy proved that for a right ideal A of S = R[x1, . . ., xk] over a ring R, if rS(A) ≠ 0 then rR(A) ≠ 0. We extend the result to the Ore extensions, the skew monoid rings and the skew power series rings over non-commutative rings and so on.
A novel route to organic-inorganic composites was described based on biomineralization of poly(ethylene glycol) (PEG)-based hydrogels. The 3-dimensional hydrogels were synthesized by radical crosslinking polymerization of poly(ethylene glycol fumarate) (PEGF) in the presence of ethylene glycol methacrylate phosphate (EGMP) as an apatite-nuclating monomer, acrylamide (AAm) as a composition-modulating comonomer, and potassium persulfate (PPS) as a radical initiator. We used the urea-mediated solution precipitation technique for biomineralization of hydrogels. The apatite grown on the surface and interior of the hydrogel was similar to biological apatites in the composition and crystalline structure. Powder x-ray diffraction (XRD) showed that the calcium phosphate crystalline platelets on hydrogels are preferentially aligned along the crystallographic c-axis direction. Inductively-coupled plasma mass spectroscopy (ICP-MS) analysis showed that the Ca/P molar ratio of apatites grown on the hydrogel template was found to be 1.60, which is identical to that of natural bones. In vitro cell experiments showed that the cell adhesion/proliferation on the mineralized hydrogel was more pronounced than on the pure polymer hydrogel.
‘Healthy Twin’ is a twin family study extension of the existing Korean Twin-Family Register. Healthy Twin recruits adult like-sex twins over the age of 30 and their adult family members. Healthy Twin protocols are primarily tailored to the study of the quantitative trait loci of complex traits as well as to the role of environment in the etiology of complex diseases. A full-length survey is underway, including questionnaires, health examinations and the collection of biological specimens. So far, 820 individuals (169 twin pairs and their families) have participated in the survey and 1068 individual twins (608 twin pairs) have replied to the mailed zygosity questionnaire as of July 2006. The first phase (2005–2006) of Healthy Twin will recruit 1550 individuals (including about 380 twin pairs), and the second phase a proposed 1500 to 2500 additional participants. We report study protocols and zygosity and the distribution of family size of the study participants.
The aim of this study was to investigate the usefulness of a three-dimensional (3D) reconstruction of computed tomography (CT) images in determining the anatomy and topographic relationship between various important structures. Using 40 ears from 20 patients with various otological diseases, a 3D reconstruction based on the image data from spiral high-resolution CT was performed by segmentation, volume-rendering and surface-rendering algorithms on a personal computer. The 3D display of the middle and inner ear structures was demonstrated in detail. Computer-assisted measurements, many of which could not be easily measured in vivo, of the reconstructed structures provided accurate anatomic details that improved the surgeon’s understanding of spatial relationships. A 3D reconstruction of temporal bone CT might be useful for education and increasing understanding of the anatomical structures of the temporal bone. However, it will be necessary to confirm the correlation between the 3D reconstructed images and histological sections through a validation study.
The aim of the present study was to determine the effect of purified high-dose anthocyanoside oligomer administration on nocturnal visual function and clinical symptoms in low-to-moderate myopia subjects. The study was a randomized, double-blind, placebo-controlled trial and involved sixty subjects with asthenopia and refractive errors between −1·00 and −8·00 diopters in both eyes. Thirty subjects were administered a purified high-dose anthocyanoside oligomer (100 mg tablet comprising 85 % anthocyanoside oligomer), and thirty were given a placebo in tablet form twice daily for 4 weeks. Prior to the treatment, the placebo and anthocyanoside groups were similar in terms of age and contrast sensitivity. Before and after treatment, subjects completed a questionnaire to determine their clinical symptoms and were also assessed for nocturnal visual function using contrast sensitivity testing. Questionnaire data analysis showed that, following treatment, twenty-two (73·3 %) anthocyanoside subjects showed improved symptoms, whereas only one placebo subject showed an improvement (Fisher's exact test, P<0·0001). Contrast sensitivity levels according to each cycle per degree significantly improved in the anthocyanoside group and remained stable in the placebo group. The mean contrast sensitivity change in the anthocyanoside group was 2·41 (SD) 1·91, compared with −0·66 (SD) 2·66 dB for the placebo group (unpaired Student's t test, P<0·0001). At all cycle per degree levels, contrast sensitivity changes in the anthocyanoside group were better than in the placebo group (unpaired Student's t test, P<0·05). The present data show that the administration of anthocyanoside oligomer appears to improve subjective symptoms and objective contrast sensitivity in myopia subjects with asthenopia.
Electroneuronography (ENoG) has become a useful test for estimating the degree of facial nerve degeneration and predicting the prognosis in patients with facial nerve palsy. Test results may be influenced by several factors, including the electrode positions, skin resistance, stimulus magnitude, and possible artifacts. Regarding recording electrode positions, different groups have used two different locations, the nasolabial fold and nasal ala. The authors compared the waveforms recorded from these two locations in ENoG recordings to obtain the optimal waveform. Twenty healthy volunteers and 25 patients with unilateral facial nerve palsy were included in this study. Recordings were carried out with the recording electrode placed on the nasolabial fold, followed by placement on the nasal ala after 10 minutes. The following parameters were assessed: (1) the supramaximal threshold, (2) amplitude and shape of the waveform, (3) interside difference, and (4) test-retest variability. There was no significant difference in the amplitude of the waveform, interside difference, and test-retest variability between the two groups. However, when the electrode was placed on the nasal ala, the threshold was significantly lower, an ideal biphasic configuration was present in almost all cases (97.5 per cent) of normal volunteers and it was easier to identify the waveform. Placement of the recording electrode on the nasal ala would be the preferred method.
Carbon nanotubes (CNTs) have attracted remarkable attention as reinforcement for composites owing to their outstanding properties1-3. CNT/Cu nanocomposites were fabricated by mixing the nano-sized Cu powders with multi-wall carbon nanotubes and followed by the spark plasma sintering process. The CNT/Cu nanocomposite fabricated from nano-sized Cu powders shows more homogeneous distribution of CNTs in matrix compared to that fabricated from macro-sized Cu powders. The hardness of CNT/Cu nanocomposite fabricated from nano-sized Cu powders increases with increasing the volume fraction of CNTs, while the hardness of that fabricated from macro-sized Cu powders decreases with the addition of CNTs.
The effect of Mg in Ag(Mg)/SiO2/Si multilayers on adhesion, agglomeration, and resistivity after annealing in vacuum at 200 to 500 have been investigated. The annealing of Ag(Mg)/SiO2/Si multilayers produced surface and interfacial MgO layers, resulting in MgO/Ag(Mg)/MgO/SiO2/Si structure. The presence of surface MgO provided the passivation against air, thus leading to the significantly enhanced resistance to agglomeration. In addition, the resistivity of Ag(Mg) film decreased by lowering Mg content and increasing the annealing temperature as well. Furthermore, Ag adhesion to SiO2 was improved due to the formation of the interfacial MgO layer resulting from the reaction of segregated Mg with SiO2. Also, the negligible solubility of Si in Ag prevented the dissolution of free silicon produced from the reaction, Mg + SiO2 = MgO + Si, which was in contrast with the dissolution of a significant amount of silicon released from the SiO2 substrate in Cu(Mg)/SiO2/Si multilayers after annealing at high temperature, e.g., 400. The dissolved Si in Cu caused the rapid increase in resistivity in Cu(Mg)/SiO2/Si.
In this study, the quality of thin film diode (TFD) as a switching device for active-matrix liquid-crystal-displays (AM-LCDs) was enhanced by low temperature annealing conditions with high reliability and good electrical properties. Device was composed with Ta as bottom electrode, anodic Ta2O5 as insulator layer and top electrode. Two types of material such as Ti and Cr were evaluated as a top electrode of the TFD device to optimize the symmetry of current-voltage characteristic curve, respectively. The annealing was done at low temperature conditions below 350°C. The low temperature annealing improved the TFD device with nearly perfect symmetry under high electric field.
We propose new poly-Si TFT's with selectively doped region in the center of channel in order to reduce large leakage current. In proposed TFT's, the selectively doped region redistributes total induced electric field in the channel. For VGS<0, VDS> 0 in the n-channel proposed TFT's, most of the high electric field applies in the depletion regions which exist the drain/undoped region and undoped region/selectively doped region which faces to the source. Comparing with conventional TFT's, the electric field induced near the drain junction reduces to about 1/2, therefore, electron-hole pairs generated in drain junction are considerably reduced. Furthermore, the ON-current of proposed TFT's is the same or slightly lower than that of conventional ones. Consequently, the experimental data show the considerable improvement of the ON/OFF current ratio.
A novel method to control the recrystallization depth of amorphous silicon (a-Si) film during the excimer laser annealing (ELA) is proposed in order to preserve a-Si that is useful for fabrication of poly-Si TFT with a-Si offset in the channel. A XeCl excimer laser beam is irradiated on a triple film structure of a-Si thin native silicon oxide (~20Å)/thick a-Si layer. Only the upper a-Si film is recrystallized by the laser beam irradiation, whereas the lower thick a-Si film remains amorphous because the thin native silicon oxide layer stops the grain growth of the poly-crystalline silicon (poly-Si). So that the thin oxide film sharply divides the upper poly-Si from the lower a-Si.
Excimer laser annealing method employing artificial nucleation seed is proposed to increase the grain size of polycrystalline silicon(poly-Si). We utilize Si component incorporated in aluminum(Al)-sputtering source for the nucleation seed. Si clusters which are to be used as nucleation seed are successfully formed on the substrate by deposition and etch-back of Si-incorporated Al layer. Irradiation of excimer laser on amorphous silicon(a-Si) film deposited on the substrate prepared by our method results in enlargement of poly-Si grains, compared with conventional laser recrystallization. Poly-Si thin film transistor also shows much improved electrical perfbrmance which directly reflects the quality of poly-Si film recrystallized by our method.
The new laser annealing technique to control the surface morphology and microstructure of poly-Si film is proposed. Compared with the conventional laser annealing technique where the laser beam is irradiated on the whole area of active layer, our new method make the laser beam transmitted locally onto the active amorphous silicon (a-Si) layer. Using the masking window in grid shape, the active layer is recrystallized in the lattice shape during the laser irradiation. By the optical microscope and scanning electron microscopy (SEM), we observed the orderly pattern, which consists of amorphous and poly-Si regions. In our new poly-Si film, the rough surface morphology, which is shown in conventional sample, could not be found. Furthermore we fabricated a poly-Si TFT utilizing the active poly-Si film recrystallized by our new method. The new poly-Si TFT showed much higher ON current than the conventional poly-Si TFT, although the leakage current is relatively high. The excellent ON characteristics may be attributed to the uniform surface morphology. After hydrogenation, the electrical characteristics of our new polySi TFT was improved considerably and this device may be applied successfully to the active matrix liquid crystal displays (AMLCD's).