650 research outputs found

    The metabolic impact of extracellular nitrite on aerobic metabolism of Paracoccus denitrificans

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    Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite / FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite / FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH dependent manner that is likely to be a result of both nitrite and free nitrous acid (FNA) (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established the Fhp to be involved in endowing nitrite / FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as NO from the internalisation of FNA

    Creative Jurisprudence: The Paradox of Free Speech Absolutism

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    Governments often seek to restrict speech on the basis of its content, navigating the ever-complex terrain between constitutional freedoms and regulatory interests. While the United States judiciary has historically endeavored to balance competing constitutional questions and government interests when scrutinizing content-based speech regulations, recent trends signify a troubling shift. The judiciary has recently embraced what this Article refers to as free speech absolutism, whereby it sidesteps the longstanding, intricate process of balancing constitutional values and public interests, in favor of an unequivocal endorsement of speech rights. This simplified judicial strategy proceeds first with an acknowledgment of the paramount importance of free speech, then shuns any form of judicial scrutiny or balancing test, instead ruling categorically in favor of speechclaimants. Such a shift represents a departure from traditional First Amendment jurisprudence, effectively ignoring tests that weigh the right to free expression against other critical constitutional values, including equality, equal protection, and nondiscrimination. This Article critically examines the choices by the judiciary, specifically the United States Supreme Court in 303 Creative v. Elenis, to adopt this free speech absolutist position. It documents the evolution of this trend, critiques its underpinnings, and proposes refinements that, if implemented, would help ensure the Court’s approach to content-based speech regulation is principled, sighted for valid government interests, and attuned to a necessary consideration of the broader spectrum of constitutional values. By doing so, it seeks to reinvigorate a more balanced and comprehensive judicial methodology that recognizes the multifaceted nature of constitutional rights and the importance of their equitable application

    The transcriptional profile of coronary arteritis in Kawasaki disease

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    BackgroundKawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.MethodsDeep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.ResultsT lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.ConclusionsThe immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies

    Arene oxidation with malonoyl peroxides

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    Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

    Thermochronology of the modern Indus River bedload: New insight into the controls on the marine stratigraphic record

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    The Indus River is the only major drainage in the western Himalaya and delivers a long geological record of continental erosion to the Arabian Sea, which may be deciphered and used to reconstruct orogenic growth if the modern bedload can be related to the mountains. In this study we collected thermochronologic data from river sediment collected near the modern delta. U-Pb ages of zircons spanning 3 Gyr show that only ∼5% of the eroding crust has been generated since India-Asia collision. The Greater Himalaya are the major source of zircons, with additional contributions from the Karakoram and Lesser Himalaya. The 39Ar/40Ar dating of muscovites gives ages that cluster between 10 and 25 Ma, differing from those recorded in the Bengal Fan. Biotite ages are generally younger, ranging 0–15 Ma. Modern average exhumation rates are estimated at ∼0.6 km/m.y. or less, and have slowed progressively since the early Miocene (∼20 Ma), although fission track (FT) dating of apatites may indicate a recent moderate acceleration in rates since the Pliocene (∼1.0 km/m.y.) driven by climate change. The 39Ar/40Ar and FT techniques emphasize the dominance of high topography in controlling the erosional flux to the ocean. Localized regions of tectonically driven, very rapid exhumation (e.g., Nanga Parbat, S. Karakoram metamorphic domes) do not dominate the erosional record

    Hyperspectral imaging for detection of corrosion on intermediate level nuclear waste containers

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    Intermediate level nuclear waste (ILW) will be stored above ground in 304L stainless steel (SS) containers for the next 100 years. During this period, the containers need to be monitored for atmospheric pitting corrosion - a known precursor of atmospherically induced stress corrosion cracking. Hyperspectral (HS) and optical imaging of pitting corrosion products from droplet experiments have been investigated towards developing a system for long term monitoring of atmospheric pitting corrosion of stainless steel containers in ILW stores. Common corrosion products were first identified via Raman spectroscopic mapping as akaganeite (β-FeOOH) and lepidocrocite (γ-FeOOH), with a secondary presence of layered double hydroxide (green rust). HS and optical methods were then compared for their efficacy at rust detection. Whilst it was not possible to identify specific corrosion species using HS imaging, HS images of rust under pitted droplets provided better contrast with the background steel than colour photography due to species having lower absorbance the near infrared (850 nm) than red (650 nm). Finally, the relationship between rust area and pit volume was determined by comparing colour photography (rust area) with confocal laser scanning microscopy (pit volume). A good correlation was present for samples exposed to a fixed relative humidity (RH) for MgCl2 droplets and CaCl2 droplets with small pit volumes. Poor correlation was found for samples exposed to natural fluctuations in RH. It was concluded that optical methods are viable for the detection of rust, but less effective for quantification of pit volumes
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