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11 Publications visible to you, out of a total of 11
Benthic Fluxes of Fluorescent Dissolved Organic Material, Salt, and Heat Measured by Multiple-Sensor Aquatic Eddy Covariance.

Abstract (Expand)

Aquatic eddy covariance (AEC) is an in situ technique for measuring fluxes in marine and freshwater systems that is based on the covariance of velocity and concentration measurements. To date, AEC has … mainly been applied to the measurement of benthic oxygen fluxes. Here, development of a fast multiple-channel sensor enables the use of AEC for measurement of benthic fluxes of fluorescent material, salt, and heat at three distinct sites in Massachusetts, USA, including the Connecticut River, the Concord River, and Upper Mystic Lake. Benthic fluxes of salt, useful as a tracer for groundwater input (submarine groundwater discharge), were consistent with independent measurements made with seepage meters. Eddy fluxes of heat were consistent with the balance of incoming solar radiation and thermal conduction at the sediment surface. Benthic eddy fluxes of fluorescent dissolved organic material (FDOM) revealed a substantial net downward flux in the humic-rich Concord River, suggesting that microbial consumption of dissolved organic carbon in the sediment was significant. Simultaneous measurement of several fluxes expands the utility of AEC as a biogeochemical tool while enabling checks for mutual consistency among data channels.

Authors: I. H. Hu, H. F. Hemond

Date Published: 20th Nov 2022

Publication Type: Journal

Novel In Vivo CometChip Reveals NDMA-Induced DNA Damage and Repair in Multiple Mouse Tissues.

Abstract (Expand)

The comet assay is a versatile assay for detecting DNA damage in eukaryotic cells. The assay can measure the levels of various types of damage, including DNA strand breaks, abasic sites and alkali-sensitive … sites. Furthermore, the assay can also be modified to include purified DNA glycosylases so that alkylated and oxidized bases can be detected. The CometChip is a higher throughput version of the traditional comet assay and has been used to study cultured cells. Here, we have tested its utility for studies of DNA damage present in vivo. We show that the CometChip is effective in detecting DNA damage in multiple tissues of mice exposed to the direct-acting methylating agent methylmethane sulfonate (MMS) and to the metabolically activated methylating agent N-nitrosodimethylamine (NDMA), which has been found to contaminate food, water, and drugs. Specifically, results from MMS-exposed mice demonstrate that DNA damage can be detected in cells from liver, lung, kidney, pancreas, brain and spleen. Results with NDMA show that DNA damage is detectable in metabolically competent tissues (liver, lung, and kidney), and that DNA repair in vivo can be monitored over time. Additionally, it was found that DNA damage persists for many days after exposure. Furthermore, glycosylases were successfully incorporated into the assay to reveal the presence of damaged bases. Overall, this work demonstrates the efficacy of the in vivo CometChip and reveals new insights into the formation and repair of DNA damage caused by MMS and NDMA.

Authors: N. A. Owiti, J. J. Corrigan, L. J. Pribyl, J. E. Kay, B. P. Engelward

Date Published: 4th Oct 2022

Publication Type: Journal

CometChip enables parallel analysis of multiple DNA repair activities.

Abstract (Expand)

DNA damage can be cytotoxic and mutagenic, and it is directly linked to aging, cancer, and other diseases. To counteract the deleterious effects of DNA damage, cells have evolved highly conserved DNA … repair pathways. Many commonly used DNA repair assays are relatively low throughput and are limited to analysis of one protein or one pathway. Here, we have explored the capacity of the CometChip platform for parallel analysis of multiple DNA repair activities. Taking advantage of the versatility of the traditional comet assay and leveraging micropatterning techniques, the CometChip platform offers increased throughput and sensitivity compared to the traditional comet assay. By exposing cells to DNA damaging agents that create substrates of Base Excision Repair, Nucleotide Excision Repair, and Non-Homologous End Joining, we show that the CometChip is an effective method for assessing repair deficiencies in all three pathways. With these applications of the CometChip platform, we expand the utility of the comet assay for precise, high-throughput, parallel analysis of multiple DNA repair activities.

Authors: J. Ge, L. P. Ngo, S. Kaushal, I. J. Tay, E. Thadhani, J. E. Kay, P. Mazzucato, D. N. Chow, J. L. Fessler, D. M. Weingeist, R. W. Sobol, L. D. Samson, S. R. Floyd, B. P. Engelward

Date Published: 9th Aug 2021

Publication Type: Journal

Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice.

Abstract (Expand)

N-Nitrosodimethylamine (NDMA) is a DNA-methylating agent that has been discovered to contaminate water, food, and drugs. The alkyladenine DNA glycosylase (AAG) removes methylated bases to initiate the … base excision repair (BER) pathway. To understand how gene-environment interactions impact disease susceptibility, we study Aag-knockout (Aag(-/-)) and Aag-overexpressing mice that harbor increased levels of either replication-blocking lesions (3-methyladenine [3MeA]) or strand breaks (BER intermediates), respectively. Remarkably, the disease outcome switches from cancer to lethality simply by changing AAG levels. To understand the underlying basis for this observation, we integrate a suite of molecular, cellular, and physiological analyses. We find that unrepaired 3MeA is somewhat toxic, but highly mutagenic (promoting cancer), whereas excess strand breaks are poorly mutagenic and highly toxic (suppressing cancer and promoting lethality). We demonstrate that the levels of a single DNA repair protein tip the balance between blocks and breaks and thus dictate the disease consequences of DNA damage.

Authors: J. E. Kay, J. J. Corrigan, A. L. Armijo, I. S. Nazari, I. N. Kohale, D. K. Torous, S. L. Avlasevich, R. G. Croy, D. N. Wadduwage, S. E. Carrasco, S. D. Dertinger, F. M. White, J. M. Essigmann, L. D. Samson, B. P. Engelward

Date Published: 16th Mar 2021

Publication Type: Journal

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