RESUMEN
Research on thermal receipts has previously focused on the toxic effects of dermal exposure from the most publicized developers (e.g., bisphenol A (BPA) and bisphenol S (BPS)), while no studies have reported on the other solvent-extractable compounds therein. Diphenyl sulfone (DPS) is a sensitizer added to thermal receipts, but little is known about DPS concentrations in receipts or potential toxicity. Here, we quantified BPA, BPS, and DPS concentrations and tentatively identified the solvent-extractable compounds of thermal receipts collected from three South Dakota (USA) cities during 2016-2017. An immortalized chicken hepatic cell line, cultured as 3D spheroids, was used to screen effects of DPS, BPS, and 17ß estradiol (E2; 0.1-1000 µM) on cell viability and gene expression changes. These chemicals elicited limited cytotoxicity with LC50 values ranging from 113 to 143 µM, and induced dysregulation in genes associated with lipid and bile acid homeostasis. Taken together, this study generated novel information on solvent-extractable chemicals from thermal receipts and toxicity data for DPS.
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Compuestos de Bencidrilo , Compuestos de Bifenilo , Fenoles , Sulfonas , Sulfonas/toxicidad , Compuestos de Bencidrilo/toxicidad , SolventesRESUMEN
Bourbon virus (BRBV) is an emerging tick-borne orthomyxovirus that causes severe febrile illness in humans. There are no specific treatments for BRBV disease currently available. Here, we developed a highly accessible and robust, quantitative fluorescence-based BRBV minigenome (MG) system and applied it to high-throughput antiviral drug screening. We demonstrated that human dihydroorotate dehydrogenase (DHODH) inhibitors, hDHODH-IN-4 and brequinar, efficiently reduced BRBV RNA synthesis, and validated these findings using infectious BRBV in vitro. The DHODH inhibitors also exhibited high potency in inhibiting MG activities of other orthomyxoviruses with emerging zoonotic potential, including bat influenza A virus, swine influenza D virus, and Thogoto virus. Our newly developed MG system is a powerful platform for antiviral drug screening across the Orthomyxoviridae family, enabling rapid development and deployment of antivirals against future emerging orthomyxoviruses.
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Thogotovirus , Garrapatas , Animales , Antivirales/farmacología , Evaluación Preclínica de Medicamentos , Ensayos Analíticos de Alto Rendimiento , Thogotovirus/genéticaRESUMEN
How life arose on the primitive Earth is one of the biggest questions in science. Biomolecular emergence scenarios have proliferated in the literature but accounting for the ubiquity of oxidized (+ 5) phosphate (PO43-) in extant biochemistries has been challenging due to the dearth of phosphate and molecular oxygen on the primordial Earth. A compelling body of work suggests that exogenous schreibersite ((Fe,Ni)3P) was delivered to Earth via meteorite impacts during the Heavy Bombardment (ca. 4.1-3.8 Gya) and there converted to reduced P oxyanions (e.g., phosphite (HPO32-) and hypophosphite (H2PO2-)) and phosphonates. Inspired by this idea, we review the relevant literature to deduce a plausible reduced phospholipid analog of modern phosphatidylcholines that could have emerged in a primordial hydrothermal setting. A shallow alkaline lacustrine basin underlain by active hydrothermal fissures and meteoritic schreibersite-, clay-, and metal-enriched sediments is envisioned. The water column is laden with known and putative primordial hydrothermal reagents. Small system dimensions and thermal- and UV-driven evaporation further concentrate chemical precursors. We hypothesize that a reduced phospholipid arises from Fischer-Tropsch-type (FTT) production of a C8 alkanoic acid, which condenses with an organophosphinate (derived from schreibersite corrosion to hypophosphite with subsequent methylation/oxidation), to yield a reduced protophospholipid. This then condenses with an α-amino nitrile (derived from Strecker-type reactions) to form the polar head. Preliminary modeling results indicate that reduced phospholipids do not aggregate rapidly; however, single layer micelles are stable up to aggregates with approximately 100 molecules.
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Meteoroides , Fósforo , Planeta Tierra , Fosfatos , FosfolípidosRESUMEN
An essential dimension of food tasting (i.e., flavor) is olfactory stimulation by volatile organic compounds (VOCs) emitted therefrom. Here, we developed a novel analytical method based on solid-phase microextraction (SPME) sampling in argon-filled gas sampling bags with direct gas chromatographyâ»mass spectrometry (GC-MS) determination to profile the volatile constituents of 31 homemade preserves prepared in South Dakota (USA) during the period 1950â»1953. Volatile profiles varied considerably, but generally decreased in detected compounds, complexity, and intensity over three successive 2-h SPME sampling periods. Volatile profiles were generally predominated by aldehydes, alcohols, esters, ketones, and organic acids, with terpenoids constituting much of the pickled cucumber volatiles. Bisphenol-A (BPA) was also serendipitously detected and then quantified in 29 samples, at levels ranging from 3.4 to 19.2 µg/kg, within the range of levels known to induce endocrine disruption effects. Absence of BPA in two samples was attributed to their lids lacking plastic liners. As the timing of their preparation coincides with the beginning of BPA incorporation into consumer products, these jars may be some of the first BPA-containing products in the USA. To the best of our knowledge, this is the first effort to characterize BPA in and volatile profiles of rare historical foods with SPME.
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Compuestos de Bencidrilo/química , Análisis de los Alimentos , Fenoles/química , Microextracción en Fase Sólida , Compuestos Orgánicos Volátiles/química , Compuestos de Bencidrilo/aislamiento & purificación , Aromatizantes/química , Alimentos en Conserva/análisis , Cromatografía de Gases y Espectrometría de Masas , Humanos , Fenoles/aislamiento & purificación , South Dakota , Compuestos Orgánicos Volátiles/aislamiento & purificaciónRESUMEN
Laboratory science requires careful maintenance of sterile reagents and tools as well as the sterilization of waste prior to disposal. However, steam autoclaves typically used for this purpose may not be readily accessible to everyone in the scientific community, such as K-12 teachers, researchers in the field, students in under-funded laboratories, or persons in the developing world who lack funding and resources. This work examines the use of commercial electric pressure cookers as an alternative method for the sterilization of media, instruments, and waste. Four commonly available brands of pressure cooker were tested for their ability to sterilize microbiological media, a variety of metal instruments, and high-titer microbial cultures. All four pressure cookers were able to sterilize these starting materials as well as a range of microbial types, including Gram-positive bacteria, Gram-negative bacteria, filamentous fungi, unicellular fungi, and mixed environmental samples. Only the Instant Pot, however, was able to sterilize autoclave tester ampoules of Geobacillus stearothermophilus spores. These results suggest that, depending on the nature of the work undertaken, store-bought pressure cookers can be an appropriate substitute for commercial autoclaves. Their adoption may also help increase the accessibility of science to a broader range of investigators.
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Esterilización/instrumentación , Medios de Cultivo , Contaminación de Equipos/prevención & control , Hongos , Bacterias Gramnegativas , Bacterias Grampositivas , Laboratorios , Presión , Esporas BacterianasRESUMEN
Multicellular development requires the careful orchestration of gene expression to correctly create and position specialized cells. In the filamentous cyanobacterium Anabaena sp. strain PCC 7120, nitrogen-fixing heterocysts are differentiated from vegetative cells in a reproducibly periodic and physiologically relevant pattern. While many genetic factors required for heterocyst development have been identified, the role of HetZ has remained unclear. Here, we present evidence to clarify the requirement of hetZ for heterocyst production and support a model where HetZ functions in the patterning stage of differentiation. We show that a clean, nonpolar deletion of hetZ fails to express the developmental genes hetR, patS, hetP and hetZ correctly and fails to produce heterocysts. Complementation and overexpression of hetZ in a hetP mutant revealed that hetZ was incapable of bypassing hetP, suggesting that it acts upstream of hetP. Complementation and overexpression of hetZ in a hetR mutant, however, demonstrated bypass of hetR, suggesting that it acts downstream of hetR and is capable of bypassing the need for hetR for differentiation irrespective of nitrogen status. Finally, protein-protein interactions were observed between HetZ and HetR, Alr2902 and HetZ itself. Collectively, this work suggests a regulatory role for HetZ in the patterning phase of cellular differentiation in Anabaena.