79 research outputs found
Photooxidants from brown carbon and other chromophores in illuminated particle extracts
While photooxidants are important in atmospheric condensed phases, there are
very few measurements in particulate matter (PM). Here we measure light
absorption and the concentrations of three photooxidants – hydroxyl radical
(⚫OH), singlet molecular oxygen (1O2*),
and oxidizing triplet excited states of organic matter (3C*) –
in illuminated aqueous extracts of wintertime particles from Davis,
California. 1O2* and 3C*, which are formed
from photoexcitation of brown carbon (BrC), have not been previously measured
in PM. In the extracts, mass absorption coefficients for dissolved organic
compounds (MACDOC) at 300 nm range between 13 000 and
30 000 cm2 (g C)−1 are approximately twice as
high as previous values in Davis fogs. The average (±1σ)⚫OH steady-state concentration in particle extracts is
4.4(±2.3)×10-16 M, which is very similar to previous values
in fog, cloud, and rain: although our particle extracts are more
concentrated, the resulting enhancement in the rate of ⚫OH
photoproduction is essentially canceled out by a corresponding enhancement in
concentrations of natural sinks for ⚫OH. In contrast,
concentrations of the two oxidants formed primarily from brown carbon (i.e.,
1O2* and 3C*) are both enhanced in the
particle extracts compared to Davis fogs, a result of higher concentrations
of dissolved organic carbon and faster rates of light absorption in the
extracts. The average 1O2* concentration in the PM extracts
is 1.6(±0.5)×10-12 M, 7 times higher than past fog
measurements, while the average concentration of oxidizing triplets is 1.0(±0.4)×10-13 M, nearly double the average Davis fog value.
Additionally, the rates of 1O2* and 3C*
photoproduction are both well correlated with the rate of sunlight
absorption.
Since we cannot experimentally measure photooxidants under ambient particle
water conditions, we measured the effect of PM dilution on oxidant
concentrations and then extrapolated to ambient particle conditions. As the
particle mass concentration in the extracts increases, measured
concentrations of ⚫OH remain relatively unchanged,
1O2* increases linearly, and 3C* concentrations increase less
than linearly, likely due to quenching by dissolved organics. Based on our
measurements, and accounting for additional sources and sinks that should be
important under PM conditions, we estimate that [⚫OH] in
particles is somewhat lower than in dilute cloud/fog drops, while [3C*]
is 30 to 2000 times higher in PM than in drops, and [1O2*] is
enhanced by a factor of roughly 2400 in PM compared to drops. Because of
these enhancements in 1O2* and 3C* concentrations,
the lifetimes of some highly soluble organics appear to be much shorter in
particle liquid water than under foggy/cloudy conditions. Based on
extrapolating our measured rates of formation in PM extracts, BrC-derived
singlet molecular oxygen and triplet excited states are overall the dominant
sinks for organic compounds in particle liquid water, with an aggregate rate
of reaction for each oxidant that is approximately 200–300 times higher
than the aggregate rate of reactions for organics with ⚫OH. For
individual, highly soluble reactive organic compounds it appears that
1O2* is often the major sink in particle water, which is a new
finding. Triplet excited states are likely also important in the fate of
individual particulate organics, but assessing this requires additional
measurements of triplet interactions with dissolved organic carbon in
natural samples.</p
Structure of Human DNA Polymerase κ Inserting dATP Opposite an 8-OxoG DNA Lesion
Background: Oxygen-free radicals formed during normal aerobic cellular metabolism attack bases in DNA and 7,8-dihydro-8-oxoguanine (8-oxoG) is one of the major lesions formed. It is amongst the most mutagenic lesions in cells because of its dual coding potential, wherein 8-oxoG(syn) can pair with an A in addition to normal base pairing of 8-oxoG(anti) with a C. Human DNA polymerase κ (Polκ) is a member of the newly discovered Y-family of DNA polymerases that possess the ability to replicate through DNA lesions. To understand the basis of Polκ\u27s preference for insertion of an A opposite 8-oxoG lesion, we have solved the structure of Polκ in ternary complex with a template-primer presenting 8-oxoG in the active site and with dATP as the incoming nucleotide.
Methodology and Principal Findings: We show that the Polκ active site is well-adapted to accommodate 8-oxoG in the syn conformation. That is, the polymerase and the bound template-primer are almost identical in their conformations to that in the ternary complex with undamaged DNA. There is no steric hindrance to accommodating 8-oxoG in the syn conformation for Hoogsteen base-paring with incoming dATP.
Conclusions and Significance: The structure we present here is the first for a eukaryotic translesion synthesis (TLS) DNA polymerase with an 8-oxoG:A base pair in the active site. The structure shows why Polκ is more efficient at inserting an A opposite the 8-oxoG lesion than a C. The structure also provides a basis for why Polκ is more efficient at inserting an A opposite the lesion than other Y-family DNA polymerases
KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species
KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell capacity to scavenge intracellular ROS through an antioxidant pathway involving FoxO1 and SOD2, thus providing novel and useful insights into the understanding of KRIT1 molecular and cellular functions
UV-visible absorption coefficients normalized to DOC of aqueous extracts of wintertime PM collected in Davis, CA, USA
Light absorption coefficients of aqueous extracts of wintertime PM collected in Davis, CA, USA
UV-visible light absorption coefficients were measured for aqueous extracts of wintertime particles from Davis, California. Full description for extraction of particles and measurement of light absorption coefficients is provided, along with the data
Pathlength normalized UV-visible absorption coefficients of aqueous extracts of wintertime PM collected in Davis, CA, USA
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