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German cockroach extract synergistically regulates tumor necrosis factor-α (TNF-α)–induced interleukin (IL)-8 expression in human airway epithelial cells. The IL-8 promoter contains nuclear factor (NF)-κB, activating protein (AP)-1, and NF for IL-6 (NF-IL6) transcription factor binding regions. Because cockroach extract activates extracellular regulated kinase (ERK), a known activator of AP-1 and NF-IL6, we focused on the regulation of these transcription factors. Although TNF-α and cockroach extract both increased AP-1 translocation, mutation of the AP-1 site in the context of the wild-type promoter had no effect on cockroach extract–induced synergy. Mutation of the NF-IL6 site in the context of the wild-type IL-8 promoter, or overexpression of a dominant-negative NF-IL6 mutant, each abolished cockroach extract–induced synergy. Cockroach extract induced NF-IL6 translocation and DNA binding, an effect that was further increased in the presence of TNF-α. Cockroach extract–induced regulation of NF-IL6 was due to active serine proteases in the extract as well as activation of protease activated receptor (PAR)-2, but not PAR-1. Chemical inhibition of ERK also attenuated cockroach extract–induced NF-IL6–DNA binding. We conclude that proteases in German cockroach extract regulate PAR-2 and ERK to increase NF-IL6 activity and synergistically regulate TNF-α–induced IL-8 promoter activity in human airway epithelium.

Background This paper contributes to the growing body of scholarship on engineering students' conceptions of core concepts in engineering, including their conception of engineering itself. Understanding how students view engineering practice can provide guidance into student responses to course features such as collaborative projects. Purpose (Hypothesis) The research question addressed in this study is: What do student portfolios reveal about student constructions of engineering? Design/Method Texts from portfolios created by mechanical engineering undergraduates were analyzed qualitatively using concepts drawn from discourse analysis. This approach makes it possible to examine conceptions through close reading of linguistic structure of a body of writing. Results Students conceived of engineering practice as “the real world,” with most students not conceiving school experiences as integral to practice. Students conceived of engineering practice in terms of strongly contrasting elements rather than as a system of intrinsic elements. Two major aspects in student conceptions were present in the portfolios: values in engineering practice and the role of other people. Largely missing also from the student discourse was the sense that engineering is inherently collaborative. Conclusion Student conceptions formed continua which bear further study to more completely characterize student views. Conceptions of engineering leaders and engineering educators deserve greater attention as well as contrasts and models for comparison to student conceptions. The benefits of understanding conceptions more completely include understanding student resistance to exercises, predicting student difficulties with exercises, and understanding the distance between what educators are trying to teach students and what students are “hearing.”

Previous studies demonstrated important interactions between the heat shock response and the I Kappa B alpha /NF- Kappa B pathway when these two pathways are induced sequentially. One such interaction involves the ability of heat shock to inhibit subsequent degradation of I Kappa B alpha in response to a proinflammatory signal. Herein we investigated the temporal relationship between recovery from heat shock and inhibition of I Kappa B alpha degradation, and the proximal mechanisms by which heat shock inhibits degradation of I Kappa B alpha in macrophages. In RAW 264.7 murine macrophages, prior heat shock inhibited LPS-mediated I Kappa B alpha degradation up to 4 h after recovery from heat shock, and this effect correlated with inhibition of LPS-mediated activation of NF- Kappa B. Beyond these recovery periods, heat shock did not inhibit I Kappa B alpha degradation. I Kappa B kinase (IKK) assays demonstrated that heat shock inhibited LPS-mediated activation of IKK up to 1 h after recovery from heat shock. Heat shock also increased intracellular phosphatase activity, and inhibition of intracellular phosphatase activity partially reversed the ability of heat shock to inhibit both LPS-mediated degradation of I Kappa B alpha and LPS-mediated activation of IKK. These data demonstrate that the ability of heat shock to inhibit degradation of I Kappa B alpha is dependent on the recovery period between the heat shock stimulus and the proinflammatory stimulus. The mechanism by which heat shock inhibits degradation of I Kappa B alpha involves dual modulation of IKK and intracellular phosphatase activity.

Previous studies demonstrated important interactions between the heat shock response and the IkappaBalpha/NF-kappaB pathway when these two pathways are induced sequentially. One such interaction involves the ability of heat shock to inhibit subsequent degradation of IkappaBalpha in response to a proinflammatory signal. Herein we investigated the temporal relationship between recovery from heat shock and inhibition of IkappaBalpha degradation, and the proximal mechanisms by which heat shock inhibits degradation of IkappaBalpha in macrophages. In RAW 264.7 murine macrophages, prior heat shock inhibited LPS-mediated IkappaBalpha degradation up to 4 h after recovery from heat shock, and this effect correlated with inhibition of LPS-mediated activation of NF-kappaB. Beyond these recovery periods, heat shock did not inhibit IkappaBalpha degradation. IkappaB kinase (IKK) assays demonstrated that heat shock inhibited LPS-mediated activation of IKK up to 1 h after recovery from heat shock. Heat shock also increased intracellular phosphatase activity, and inhibition of intracellular phosphatase activity partially reversed the ability of heat shock to inhibit both LPS-mediated degradation of IkappaBalpha and LPS-mediated activation of IKK. These data demonstrate that the ability of heat shock to inhibit degradation of IkappaBalpha is dependent on the recovery period between the heat shock stimulus and the proinflammatory stimulus. The mechanism by which heat shock inhibits degradation of IkappaBalpha involves dual modulation of IKK and intracellular phosphatase activity.

Previous studies demonstrated important interactions between the heat shock response and the IkappaBalpha/NF-kappaB pathway when these two pathways are induced sequentially. One such interaction involves the ability of heat shock to inhibit subsequent degradation of IkappaBalpha in response to a proinflammatory signal. Herein we investigated the temporal relationship between recovery from heat shock and inhibition of IkappaBalpha degradation, and the proximal mechanisms by which heat shock inhibits degradation of IkappaBalpha in macrophages. In RAW 264.7 murine macrophages, prior heat shock inhibited LPS-mediated IkappaBalpha degradation up to 4 h after recovery from heat shock, and this effect correlated with inhibition of LPS-mediated activation of NF-kappaB. Beyond these recovery periods, heat shock did not inhibit IkappaBalpha degradation. IkappaB kinase (IKK) assays demonstrated that heat shock inhibited LPS-mediated activation of IKK up to 1 h after recovery from heat shock. Heat shock also increased intracellular phosphatase activity, and inhibition of intracellular phosphatase activity partially reversed the ability of heat shock to inhibit both LPS-mediated degradation of IkappaBalpha and LPS-mediated activation of IKK. These data demonstrate that the ability of heat shock to inhibit degradation of IkappaBalpha is dependent on the recovery period between the heat shock stimulus and the proinflammatory stimulus. The mechanism by which heat shock inhibits degradation of IkappaBalpha involves dual modulation of IKK and intracellular phosphatase activity.

Purpose Research has shown that mind–body practices like meditation and yoga can improve quality of life among female cancer survivors. Yet, correlates of the likelihood to use these practices are unknown in the USA. The goal of this study was to use recent data from the 2022 National Health Interview Survey (NHIS) to establish the prevalence and correlates of meditation and yoga practices among female cancer survivors in the USA, as well as among survivors who report high or frequent anxiety. Methods Using data from the NHIS, we identified eligible female respondents who had reported being diagnosed with cancer ( N  = 1,945). We identified factors associated with meditation and yoga practice use through self-reported surveys. Results Our sample ( N  = 1945) was primarily White (82.9%), 65 years or older (55.2%), heterosexual (97.2%), lived in medium/small metro areas (35.3%) in the South (36.6%), did not report frequent or high anxiety (63.9%), 21.5% used meditation, and 16.8% used yoga. Our results showed that among female survivors with high or frequent anxiety, there were higher odds of using yoga among those living in large central metro areas or who reported other cancers. Conclusion Use of meditation and yoga practices after cancer diagnosis remains uncommon. To best reach diverse survivors who may benefit from evidence-based mind–body practices, tailoring may be needed.

Current approaches do not eliminate all HIV-1 maternal-to-infant transmissions (MTIT); new prevention paradigms might help avert new infections. We administered Maraviroc (MVC) to rhesus macaques (RMs) to block CCR5-mediated entry, followed by repeated oral exposure of a CCR5-dependent clone of simian immunodeficiency virus (SIV)mac251 (SIVmac766). MVC significantly blocked the CCR5 coreceptor in peripheral blood mononuclear cells and tissue cells. All control animals and 60% of MVC-treated infant RMs became infected by the 6th challenge, with no significant difference between the number of exposures (p=0.15). At the time of viral exposures, MVC plasma and tissue (including tonsil) concentrations were within the range seen in humans receiving MVC as a therapeutic. Both treated and control RMs were infected with only a single transmitted/founder variant, consistent with the dose of virus typical of HIV-1 infection. The uninfected RMs expressed the lowest levels of CCR5 on the CD4+ T cells. Ramp-up viremia was significantly delayed (p=0.05) in the MVC-treated RMs, yet peak and postpeak viral loads were similar in treated and control RMs. In conclusion, in spite of apparent effective CCR5 blockade in infant RMs, MVC had marginal impact on acquisition and only a minimal impact on post infection delay of viremia following oral SIV infection. Newly developed, more effective CCR5 blockers may have a more dramatic impact on oral SIV transmission than MVC.