Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure

The role of social support and social networks in smoking behavior among middle and older aged people in rural areas of South Korea: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although the number of studies on anti-smoking interventions has increased, studies focused on identifying social contextual factors in rural areas are scarce. The purpose of this study was to explore the role of social support and social networks in smoking behavior among middle and older aged people living in rural areas of South Korea.</p> <p>Methods</p> <p>The study employed a cross-sectional design. Participants included 1,057 adults, with a mean age of 60.7 years, residing in rural areas. Information on participants' tobacco use, stress, social support, and social networks was collected using structured questionnaires. The chi-square test, the t-test, ANOVA, and logistic regression were used for data analysis.</p> <p>Results</p> <p>The overall smoking prevalence in the study was 17.4% (men, 38.8%; women, 5.1%). Overall, stress was high among women, and social support was high among men. Smokers had high levels of social support (t = -2.90, p = .0038) and social networks (t = -2.22, p = .0271), as compared to non- and former smokers. Those in the high social support group were likely to be smokers (AOR = 2.21, 95% CI 1.15-4.26). Women with moderate social ties were less likely to smoke (AOR = 0.18, 95% CI 0.05-0.61).</p> <p>Conclusion</p> <p>There was a protective role of a moderate social network level among women, and a high level of social support was associated with smoking behaviors in rural areas. Findings suggest the need for a comprehensive understanding of the functions and characteristics of social contextual factors including social support and social networks in order to conduct more effective anti-smoking interventions in rural areas.</p

A novel family VII esterase with industrial potential from compost metagenomic library

<p>Abstract</p> <p>Background</p> <p>Among the vast microbial genomic resources now available, most microbes are unculturable in the laboratory. A culture-independent metagenomic approach is a novel technique that circumvents this culture limitation. For the screening of novel lipolytic enzymes, a metagenomic library was constructed from compost, and the clone of <it>estCS2 </it>was selected for lipolytic properties on a tributyrin-containing medium.</p> <p>Results</p> <p>The <it>estCS2 </it>sequence encodes a protein of 570 amino acid residues, with a predicted molecular mass of 63 kDa, and based on amino acid identity it most closely matches (45%) the carboxylesterase from <it>Haliangium ochraceum </it>DSM 14365. EstCS2 belong to family VII, according to the lipolytic enzyme classification proposed by Arpigny and Jaeger, and it retains the catalytic triad Ser₂₄₅-Glu₃₆₃-His₄₆₆that is typical of an α/β hydrolase. The Ser₂₄₅residue in the catalytic triad of EstCS2 is located in the consensus active site motif GXSXG. The EstCS2 exhibits strong activity toward <it>p</it>-nitrophenyl caproate (C6), and it is stable up to 60°C with an optimal enzymatic activity at 55°C. The maximal activity is observed at pH 9, and it remains active between pH 6-10. EstCS2 shows remarkable stability in up to 50% (v/v) dimethyl sulfoxide (DMSO) or dimethylformamide (DMF). The enzyme has the ability to cleave sterically hindered esters of tertiary alcohol, as well as to degrade polyurethanes, which are widely used in various industries.</p> <p>Conclusions</p> <p>The high stability of EstCS2 in organic solvents and its activity towards esters of ketoprofen and tertiary alcohols, and in polyurethane suggests that it has potential uses for many applications in biotransformation and bioremediation.</p

Identification and characterization of Rv3281 as a novel subunit of a biotin-dependent Acyl-CoA carboxylase in Mycobacterium tuberculosis H37Rv

Mycobacterium tuberculosis produces a large number of structurally diverse lipids generated from the carboxylation products of acetyl-CoA and propionyl-CoA. A biotin-dependent acyl-CoA carboxylase was purified from M. tuberculosis H37Rv by avidin affinity chromatography, and the three major protein components were determined by N-terminal sequencing to be the 63-kDa alpha 3-subunit (AccA3, Rv3285), the 59-kDa beta 5-subunit (AccD5, Rv3280), and the 56-kDa beta 4-subunit (AccD4, Rv3799). A minor protein of about 24 kDa that co-purified with the above subunits was identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to be the product of Rv3281 that is located immediately downstream of the open reading frame encoding the beta 5-subunit. This protein displays identity over a short stretch of amino acids with the recently discovered epsilon-subunits of Streptomyces coelicolor, suggesting that it might be an epsilon-subunit of the mycobacterial acyl-CoA carboxylase. To test this hypothesis, the carboxylase subunits were expressed in Escherichia coli and purified. Acyl-CoA carboxylase activity was successfully reconstituted for the first time from purified subunits of the acyl-CoA carboxylase of M. tuberculosis. The reconstituted alpha 3-beta 5 showed higher activity with propionyl-CoA than with acetyl-CoA, and the addition of the epsilon-subunit stimulated the carboxylation by 3.2- and 6.3-fold, respectively. The alpha 3-beta 4 showed very low activity with the above substrates but carboxylated long chain acyl-CoA. This epsilon-subunit contains five sets of tandem repeats at the N terminus that are required for maximal enhancement of carboxylase activity. The Rv3281 open reading frame is co-transcribed with Rv3280 in the mycobacterial cell, and the level of epsilon-protein was highest during the log phase and decreased during the stationary phase

Query-Efficient Black-Box Red Teaming via Bayesian Optimization

The deployment of large-scale generative models is often restricted by their potential risk of causing harm to users in unpredictable ways. We focus on the problem of black-box red teaming, where a red team generates test cases and interacts with the victim model to discover a diverse set of failures with limited query access. Existing red teaming methods construct test cases based on human supervision or language model (LM) and query all test cases in a brute-force manner without incorporating any information from past evaluations, resulting in a prohibitively large number of queries. To this end, we propose Bayesian red teaming (BRT), novel query-efficient black-box red teaming methods based on Bayesian optimization, which iteratively identify diverse positive test cases leading to model failures by utilizing the pre-defined user input pool and the past evaluations. Experimental results on various user input pools demonstrate that our method consistently finds a significantly larger number of diverse positive test cases under the limited query budget than the baseline methods. The source code is available at https://github.com/snu-mllab/Bayesian-Red-Teaming.Comment: ACL 2023 Long Paper - Main Conferenc

Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2–IL-6 axis

Background Mounting evidence suggests that the immune system plays detrimental or protective roles in nerve injury and repair. Main body Herein we report that both CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells are required to protect corneal nerves against sterile corneal injury. Selective depletion of CD11bhiLy6Ghi or CD11bhiLy6ChiLy6Glo cells resulted in aggravation of corneal nerve loss, which correlated with IL-6 upregulation. IL-6 neutralization preserved corneal nerves while reducing myeloid cell recruitment. IL-6 replenishment exacerbated corneal nerve damage while recruiting more myeloid cells. In mice lacking Toll-like receptor 2 (TLR2), the levels of IL-6 and myeloid cells were decreased and corneal nerve loss attenuated, as compared to wild-type and TLR4 knockout mice. Corneal stromal fibroblasts expressed TLR2 and produced IL-6 in response to TLR2 stimulation. Conclusion Collectively, our data suggest that CD11bhiLy6Ghi and CD11bhiLy6ChiLy6Glo myeloid cells confer corneal nerve protection under sterile injury by creating a negative-feedback loop to suppress the upstream TLR2–IL-6 axis that drives corneal nerve loss

Linear Wave Reflection by Trench with Various Shapes

author's final versionTwo types of analytical solutions for waves propagating over an asymmetric trench are derived. One is a shallow water wave model and the other is an extended model applicable to deeper water. The water depth inside the trench varies in proportion to a power of distance from the center of the trench (where the center means the deepest water depth point and the origin of -coordinate in this study). The mild-slope equation is transformed into a second order ordinary differential equation with variable coefficients based on the longwave assumption or Hunts (1979) approximate solution for wave dispersion. The analytical solutions are then obtained by using the power series technique. The analytical solutions are compared with the numerical solution of the hyperbolic mild-slope equations. After obtaining the analytical solutions under various conditions, the results are analyzed