159 research outputs found
GW150914 and gravitational-wave astronomy
On September 14, 2015, the first detection of gravitational waves at the advanced Laser Interferometer Gravitational- Wave Observatory (LIGO) detectors, in the United States, marked the beginning of "gravitational-wave astronomy", that opens a new window looking into the violent sides of our Universe. It is very promising that at other wavelengths detections of gravitational waves with various space-based and ground-based observatories will show up in the near future of this century. These observatories include space-based laser interferometer antennas, pulsar timing arrays, cosmic microwave background satellites, etc
Thiopeptide Antibiotics Exhibit a Dual Mode of Action against Intracellular Pathogens by Affecting Both Host and Microbe
SummaryThiostrepton (TSR) is an archetypal thiopeptide antibiotic possessing a quinaldic acid (QA) moiety in the side ring system. According to the mechanism of TSR previously known to target bacterial ribosome, we recently designed and biosynthesized several TSR derivatives that varied in QA substitution. Utilizing these thiopeptide antibiotics to treat the intracellular pathogen Mycobacterium marinum, we herein report a novel mode of action of TSRs, which induce ER stress-mediated autophagy to enhance host cell defense. This intracellular response, which is sensitive to the modification of the QA group, serves as an indirect but unignorable mechanism for eliminating intracellular pathogens. TSRs are thus the only type of antibiotics, to our knowledge, with the dual action on both the parasitic bacteria and the infected host cells. The newly observed mechanism of TSRs may inspire the future change in the treatment of intracellular pathogens, by taking host response into account
Cerium doped copper/ZSM-5 catalysts used for the selective catalytic reduction of nitrogen oxide with ammonia
The CuCe/ZSM-5 catalysts with different cerium loadings (0, 0.5, 1.0, 1.5 and 2.0wt.%) was investigated to evaluate the correlation between structural characteristics and catalytic performance for the selective catalytic reduction (SCR) of NO by NH3. It was found that the addition of cerium increased copper dispersion and prevented its crystallization. According to the results of X-ray photoelectron spectroscopy (XPS) and temperature-programmed reduction by hydrogen (H2-TPR), copper species were enriched on the ZSM-5 grain surfaces and part of copper ions was incorporated into the cerium lattice. Addition of cerium improved the redox properties of the CuCe/ZSM-5 catalysts, owing to the higher valence of copper and mobility of lattice oxygen than those of Cu/ZSM-5 catalyst. Hence the introduction of cerium in Cu/ZSM-5 improved significantly NO conversion. On the one hand, the cerium introduction into Cu-Z enhances their low-temperature activities. 95% NO conversion is reached around 197°C for Cu-Z while the corresponding temperature value decreases to 148°C for CuCe4-Z. On the other hand, the temperature range of efficient NO reduction (95%) also extends to higher temperature when the cerium are added to Cu/ZSM-5. Among the Cu-Ce/ZSM-5 catalysts tested, the CuCe4-Z sample exhibits the highest catalytic activity with the temperature range for 90% NO removal of 148-427°C
A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis
<p>Abstract</p> <p>Background</p> <p>The first report on the transferable, plasmid-mediated quinolone-resistance determinant <it>qnrA1 </it>was in 1998. Since then, <it>qnr </it>alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP) family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural arrangement.</p> <p>Results</p> <p>We conducted random and site-directed mutagenesis on <it>qnrA1 </it>and on <it>qnrC</it>, a newly identified quinolone-resistance gene from <it>Proteus mirabilis</it>. Many of the Qnr mutants lost their quinolone resistance function. The highly conserved hydrophobic Leu or Phe residues at the center of the pentapeptide repeats are known as <it>i </it>sites, and loss-of-function mutations included replacement of the <it>i </it>site hydrophobic residues with charged residues, replacing the <it>i</it><sup>-2 </sup>site, N-terminal to the <it>i </it>residues, with bulky side-chain residues, introducing Pro into the β-helix coil, deletion of the N- and C-termini, and excision of a central coil. Molecular dynamics simulations and homology modeling demonstrated that QnrC overall adopts a stable β-helix fold and shares more similarities with MfpA than with other PRP structures. Based on homology modeling and molecular dynamics simulation, the dysfunctional point mutations introduced structural deformations into the quadrilateral β-helix structure of PRPs. Of the pentapeptides of QnrC, two-thirds adopted a type II β-turn, while the rest adopted type IV turns. A gap exists between coil 2 and coil 3 in the QnrC model structure, introducing a structural flexibility that is similar to that seen in MfpA.</p> <p>Conclusion</p> <p>The hydrophobic core and the β-helix backbone conformation are important for maintaining the quinolone resistance property of Qnr proteins. QnrC may share structural similarity with MfpA.</p
An Operational Statistical Scheme for Tropical Cyclone-Induced Rainfall Forecast
Nonparametric methods are used in this study to analyze and predict short-term rainfall due to tropical cyclones (TCs) in a coastal meteorological station. All 427 TCs during 1953–2011, which made landfall along the Southeast China coast with a distance less than 700 km to a certain meteorological station, Shenzhen, are analyzed and grouped according to their landfalling direction, distance, and intensity. The corresponding daily rainfall records at Shenzhen Meteorological Station (SMS) during TCs landfalling period (a couple of days before and after TC landfall) are collected. The maximum daily rainfall (R24) and maximum 3-day accumulative rainfall (R72) records at SMS for each TC category are analyzed by a nonparametric statistical method, percentile estimation. The results are plotted by statistical boxplot, expressing in the probability of precipitation. The performance of the statistical boxplots was evaluated to forecast the short-term rainfall at SMS during the TC seasons in 2012 and 2013. The results show that the boxplot scheme can be used as a valuable reference to predict the short-term rainfall at SMS due to TCs landfalling along the Southeast China coast
Left-Side Bias Is Observed in Sequential Matching Paradigm for Face Processing
The left-side bias refers to how a chimeric face is created from the left side of a face (from the viewer’s perspective) and its mirror image are considered more similar to the original face than a chimeric face created from the right side of the same face and its mirror image. Previous studies investigated the left-side bias by using the chimeric stimuli task, where the original face and chimeric face were presented simultaneously. However, it remains unclear whether left-side bias effect is observed when the original face and chimeric face are presented sequentially. We completed two experiments using the sequential matching paradigm to investigate this issue. The results from both Experiment 1 and 2 showed that participants judged the identical proportion of the left chimeric face and original face was significantly higher than that of the right chimeric face and original face, which implies that the left-side bias effect can be observed in the sequential matching paradigm for face processing
The chinese herbal decoction danggui buxue tang inhibits angiogenesis in a rat model of liver fibrosis.
In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction Danggui Buxue Tang (DBT; Radix Astragali and Radix Angelicae sinensis in 5 : 1 ratio) in a rat model of liver fibrosis, in order to elucidate its mechanisms of action against liver fibrosis. Liver fibrosis was induced with CCl(4) and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and 8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of VEGF, Ang1 and TGF-β1 and their signaling mediators, whereas NAC had no effect on VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1α gene and protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1α in fibrotic livers
Herbal Compound “Jiedu Huayu” Reduces Liver Injury in Rats via Regulation of IL-2, TLR4, and PCNA Expression Levels
Aim of the Study. To investigate the preventative effects of Jiedu Huayu (JDHY) on D-galactosamine (D-GalN) and lipopolysaccharide-induced acute liver failure (ALF) and to evaluate the possible mechanisms of action. Materials and Methods. ALF was induced in Wistar rats by administrating D-GalN (900 mg/kg) and lipopolysaccharide (10 μg/kg). After treatment with JDHY granules, the levels of blood alanine aminotransferase, aspartate aminotransferase, total bilirubin, and prothrombin time were determined. Proliferating cell nuclear antigen was detected by immunohistochemistry staining. The expression of interleukin-2 (IL-2) and toll-like receptor 4 (TLR4) was examined by fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. Results. JDHY treatment dramatically improved liver function and increased survival rates in an ALF model in rats. We observed a decrease in IL-2 and TLR4 expression following treatment with JDHY in liver cells from ALF rats using qRT-PCR and Western blot analysis. Conclusion. We hypothesize that the therapeutic potential of JDHY for treating ALF is due to its modulatory effect on the suppression of inflammation and by promoting hepatocyte regeneration. Our results contribute towards validation of the traditional use of JDHY in the treatment of liver disease
Salvianolic Acid B Attenuates Rat Hepatic Fibrosis via Downregulating Angiotensin II Signaling
The renin-angiotensin system (RAS) plays an important role in hepatic fibrosis. Salvianolic acid B (Sal B), one of the water-soluble components from Radix Salviae miltiorrhizae, has been used to treat hepatic fibrosis, but it is still not clear whether the effect of Sal B is related to angiotensin II (Ang II) signaling pathway. In the present study, we studied Sal B effect on rat liver fibrosis and Ang-II related signaling mediators in dimethylnitrosamine-(DMN-) induced rat fibrotic model in vivo and Ang-II stimulated hepatic stellate cells (HSCs) in vitro, with perindopril or losartan as control drug, respectively. The results showed that Sal B and perindopril inhibited rat hepatic fibrosis and reduced expression of Ang II receptor type 1 (AT1R) and ERK activation in fibrotic liver. Sal B and losartan also inhibited Ang II-stimulated HSC activation including cell proliferation and expression of type I collagen I (Col-I) and α-smooth muscle actin (α-SMA) production in vitro, reduced the gene expression of transforming growth factor beta (TGF-β), and downregulated AT1R expression and ERK and c-Jun phosphorylation. In conclusion, our results indicate that Sal B may exert an antihepatic fibrosis effect via downregulating Ang II signaling in HSC activation
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KIF21A Mutations in Two Chinese Families with Congenital Fibrosis of the Extraocular Muscles (CFEOM)
Purpose: Two Chinese families (XT and YT) with congenital fibrosis of the extraocular muscles (CFEOM) were identified. The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees. Methods: Clinical characterization and genetic studies were performed. Microsatellite genotyping for linkage to the CFEOM1 and CFEOM3 loci was performed. The probands were screened for KIF21A mutations by bidirectional direct sequencing. Once a mutation was detected in the proband, all other participating family members and 100 unrelated control normal individuals were screened for the mutation. Results: All affected individuals in family XT shared the common manifestations of CFEOM1. Family YT had two affected individuals, a mother and a daughter. The daughter had CFEOM1, while her mother never had congential ptosis but did have limited extraocular movements status post strabismus surgery. Haplotype analysis revealed that pedigree XT was linked to the 12q CFEOM1 locus and the affected memberes harbored the second most common missense mutation in KIF21A (2,861G>A, R954Q). Family YT harbored the most common missense de novo mutation in KIF21A (2,860C>T, R954W). Both of these mutations have been previously described. Conclusions: The observation of these two KIF21A mutations in a Chinese pedigree underscores the homogeneity of these mutations as a cause of CFEOM1 and CFEOM3 across ethnic divisions
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