242 research outputs found
Expression of Human Microsomal Epoxide Hydrolase in Saccharomyces cerevisiae Reveals a Functional Role in Aflatoxin B1 Detoxification
The metabolism and genotoxicity of the carcinogenic mycotoxin, aflatoxin B1 (AFB), was studied in the lower eukaryotic yeast Saccharomyces cerevisiae. Recombinant strains of yeast were engineered to express human cDNAs for CYP1A1, CYP1A2, and microsomal epoxide hydrolase (mEH). Coexpression of mEH with CYP1A1 or CYP1A2 resulted in significant decreases in measurements of AFB genotoxicity. In cells expressing CYP1A2 and mEH, the level of AFB-DNA adducts was decreased by 50% relative to cells expressing CYP1A2 alone. Mitotic recombination, as assayed by gene conversion at thetrp5locus, was diminished by 50% or greater in cells coexpressing mEH and CYP1A2 compared to CYP1A2 alone. The mutagenicity of AFB in the Ames assay was also decreased by approximately 50% when AFB was incubated with microsomes containing CYP1A1 or CYP1A2 and mEH versus CYP1A1 or CYP1A2 alone. The biotransformation of AFB by CYPs is known to involve the generation of a reactive epoxide intermediate, AFB-8,9-epoxide, but previous direct biochemical and kinetic studies have failed to demonstrate any functional role for mEH in AFB detoxification. By reconstructing a metabolic pathway in intact yeast, we have shown, for the first time, that mEH may play a role in mitigating the carcinogenic effects of AF
Variations in Implementation of Specifications Grading in STEM Courses
Specifications grading is an assessment strategy based on mastery learning, clear learning objectives, and frequent evaluations and feedback. Twelve instructors at a southeastern four-year public college implemented the specifications grading method across eight discrete courses in four STEM areas. In this modified assessment strategy, the students controlled their grades through multiple attempts, with limitations, on assessments of course objectives. The instructors designed and executed specifications grading in unique ways that aligned with their content areas, teaching beliefs, and individual teaching styles.
Preliminary observations suggest that, regardless of subject area, specifications grading can be used as an alternative to traditional assessment methodologies in STEM courses, regardless of the content area. In general, three major variations of implementation arose from this initial trial. Major differences and commonalities among these types are discussed as they relate to the course subject area in which they are used. The results of this work add a unique set of assessment practices to the current body of knowledge in that other practitioners may gain insight on variations of the specifications grading method that may be practical and applicable in their own classrooms
On the Regularizability of the Big Bang Singularity
The singularity for the big bang state can be represented using the
generalized anisotropic Friedmann equation, resulting in a system of
differential equations in a central force field. We study the regularizability
of this singularity as a function of a parameter, the equation of state, .
We prove that for it is regularizable only for satisfying relative
prime number conditions, and for it can always be regularized. This
is done by using a McGehee transformation, usually applied in the three and
four-body problems. This transformation blows up the singularity into an
invariant manifold. The relationship of this result to other cosmological
models is briefly discussed.Comment: 22 pages, 0 figure
Identification and quantification of protein S-nitrosation by nitrite in the mouse heart during ischemia.
Nitrate (NO3-) and nitrite (NO2-) are known to be cardioprotective and to alter energy metabolism in vivo NO3- action results from its conversion to NO2- by salivary bacteria, but the mechanism(s) by which NO2- affects metabolism remains obscure. NO2- may act by S-nitrosating protein thiols, thereby altering protein activity. But how this occurs, and the functional importance of S-nitrosation sites across the mammalian proteome, remain largely uncharacterized. Here we analyzed protein thiols within mouse hearts in vivo using quantitative proteomics to determine S-nitrosation site occupancy. We extended the thiol-redox proteomic technique, isotope-coded affinity tag labeling, to quantify the extent of NO2--dependent S-nitrosation of proteins thiols in vivo Using this approach, called SNOxICAT (S-nitrosothiol redox isotope-coded affinity tag), we found that exposure to NO2- under normoxic conditions or exposure to ischemia alone results in minimal S-nitrosation of protein thiols. However, exposure to NO2- in conjunction with ischemia led to extensive S-nitrosation of protein thiols across all cellular compartments. Several mitochondrial protein thiols exposed to the mitochondrial matrix were selectively S-nitrosated under these conditions, potentially contributing to the beneficial effects of NO2- on mitochondrial metabolism. The permeability of the mitochondrial inner membrane to HNO2, but not to NO2-, combined with the lack of S-nitrosation during anoxia alone or by NO2- during normoxia places constraints on how S-nitrosation occurs in vivo and on its mechanisms of cardioprotection and modulation of energy metabolism. Quantifying S-nitrosated protein thiols now allows determination of modified cysteines across the proteome and identification of those most likely responsible for the functional consequences of NO2- exposure
Training of Instrumentalists and Development of New Technologies on SOFIA
This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal
Survey (Astro2010)1 Committee on the State of the Profession to emphasize the
potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to
contribute to the training of instrumentalists and observers, and to related
technology developments. This potential goes beyond the primary mission of
SOFIA, which is to carry out unique, high priority astronomical research.
SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable
astronomical observations anywhere, any time, and at most wavelengths between
0.3 microns and 1.6 mm not accessible from ground-based observatories. These
attributes, accruing from the mobility and flight altitude of SOFIA, guarantee
a wealth of scientific return. Its instrument teams (nine in the first
generation) and guest investigators will do suborbital astronomy in a
shirt-sleeve environment. The project will invest $10M per year in science
instrument development over a lifetime of 20 years. This, frequent flight
opportunities, and operation that enables rapid changes of science instruments
and hands-on in-flight access to the instruments, assure a unique and extensive
potential - both for training young instrumentalists and for encouraging and
deploying nascent technologies. Novel instruments covering optical, infrared,
and submillimeter bands can be developed for and tested on SOFIA by their
developers (including apprentices) for their own observations and for those of
guest observers, to validate technologies and maximize observational
effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on
State of the Professio
Cardiorespiratory fitness levels and body mass index of pre-adolescent children and older adults during the COVID-19 pandemic
IntroductionThe social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children.MethodsHealthy older individuals (N = 593; 65–80 years) and 200 typically developing children (8–10 years) completed a graded maximal exercise test and had their height and weight measured.ResultsResults revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness.DiscussionResults from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition.Clinical trial registrationOlder adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238
Measuring electromagnetic fields (EMF) around wind turbines in Canada: is there a human health concern?
Adipose-derived mesenchymal stem cells from the sand rat: transforming growth factor beta and 3D co-culture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix
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