20 research outputs found

    Biogenic carbonate mercury and marine temperature records reveal global influence of Late Cretaceous Deccan Traps

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155784/1/Meyer_et_al_2019_Biogenic_carbonate_mercury.pd

    Comprehensive Analysis Reveals Dynamic and Evolutionary Plasticity of Rab GTPases and Membrane Traffic in Tetrahymena thermophila

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    Cellular sophistication is not exclusive to multicellular organisms, and unicellular eukaryotes can resemble differentiated animal cells in their complex network of membrane-bound structures. These comparisons can be illuminated by genome-wide surveys of key gene families. We report a systematic analysis of Rabs in a complex unicellular Ciliate, including gene prediction and phylogenetic clustering, expression profiling based on public data, and Green Fluorescent Protein (GFP) tagging. Rabs are monomeric GTPases that regulate membrane traffic. Because Rabs act as compartment-specific determinants, the number of Rabs in an organism reflects intracellular complexity. The Tetrahymena Rab family is similar in size to that in humans and includes both expansions in conserved Rab clades as well as many divergent Rabs. Importantly, more than 90% of Rabs are expressed concurrently in growing cells, while only a small subset appears specialized for other conditions. By localizing most Rabs in living cells, we could assign the majority to specific compartments. These results validated most phylogenetic assignments, but also indicated that some sequence-conserved Rabs were co-opted for novel functions. Our survey uncovered a rare example of a nuclear Rab and substantiated the existence of a previously unrecognized core Rab clade in eukaryotes. Strikingly, several functionally conserved pathways or structures were found to be associated entirely with divergent Rabs. These pathways may have permitted rapid evolution of the associated Rabs or may have arisen independently in diverse lineages and then converged. Thus, characterizing entire gene families can provide insight into the evolutionary flexibility of fundamental cellular pathways

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Changes in the mercury isotopic composition of sediments from a remote alpine lake in Wyoming, USA

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155779/1/Kurz_et_al_2019_Changes.pd

    Spatial and temporal variation in the isotopic composition of mercury in the South River, VA

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155767/1/Washburn_et_al_2018_Spacial_and_temporal_variation.pd

    Spatiotemporal characterization of mercury isotope baselines and anthropogenic influences in lake sediment cores

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    A recent consensus from the literature suggests that increasing temporal trends in mercury isotope ratios in lake sediment cores from pre-industrial (1510 – 1850) to present-day (1990 – 2014) is a global phenomenon. While multiple hypotheses have been proposed regarding this widespread phenomenon, local to global scale changes including increased anthropogenic mercury emissions, climate change, and changes in atmospheric composition have made it difficult to decipher between source- and processes-driven changes for mercury. Through compilation of mercury concentration (THg) and mercury isotope ratios in twenty-two lake sediment cores collected from around the world, we explore reasons for the observed increase in mercury isotope ratio. In contrary to the consensus, we find that the increasing temporal trend in Δ199Hg is not a global phenomenon. Instead, a widespread phenomenon is the increasing δ202Hg together with mercury concentration in lake sediment cores from pre-industrial to present-day period. This can be explained by increased contribution of modern-day anthropogenic mercury emission sources, which have much higher δ202Hg (-0.9 to -0.3‰) compared to pre-industrial sediments (-1.55±0.96‰). The increasing trends in Δ199Hg were observed in fifteen lake sediment cores, which have low pre-industrial Δ199Hg (-0.20±0.32‰) compared to the sediment cores with near-zero to positive pre-industrial Δ199Hg (0.08±0.07‰). No correlation was found between the magnitudes of δ202Hg (r2 = 0.09) and Δ199Hg (r2 = 0.20, both p > 0.05) changes from pre-industrial to present-day with that of THg. This suggests that, rather than the extent of mercury input to the lake system, the magnitudes of δ202Hg and Δ199Hg changes are determined by the pre-industrial or baseline δ202Hg and Δ199Hg in the sediment cores. Our study suggests that the characterization of baseline mercury isotope ratios is critical for interpreting the observed temporal trends in sediment core mercury isotope ratios. Our study also suggests that sediment δ202Hg can be used as an important proxy for monitoring changes in anthropogenic mercury sources and for evaluating the effectiveness of the Minamata Convention on Mercury.1

    The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX.

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    The ataxia-telangiectasia mutated (ATM) protein kinase is activated in response to ionizing radiation (IR) and activates downstream DNA-damage signaling pathways. Although the role of ATM in the cellular response to ionizing radiation has been well characterized, its role in response to other DNA-damaging agents is less well defined. We previously showed that genistein, a naturally occurring isoflavonoid, induced increased ATM protein kinase activity, ATM-dependent phosphorylation of p53 on serine 15 and activation of the DNA-binding properties of p53. Here, we show that genistein also induces phosphorylation of p53 at serines 6, 9, 20, 46, and 392, and that genistein-induced accumulation and phosphorylation of p53 is reduced in two ATM-deficient human cell lines. Also, we show that genistein induces phosphorylation of ATM on serine 1981 and phosphorylation of histone H2AX on serine 139. The related bioflavonoids, daidzein and biochanin A, did not induce either phosphorylation of p53 or ATM at these sites. Like genistein, quercetin induced phosphorylation of ATM on serine 1981, and ATM-dependent phosphorylation of histone H2AX on serine 139; however, p53 accumulation and phosphorylation on serines 6, 9, 15, 20, 46, and 392 occurred in ATM-deficient cells, indicating that ATM is not required for quercetin-induced phosphorylation of p53. Our data suggest that genistein and quercetin induce different DNA-damage induced signaling pathways that, in the case of genistein, are highly ATM-dependent but, in the case of quercetin, may be ATM-dependent only for some downstream target

    Isotopic Characterization of Mercury Downstream of Historic Industrial Contamination in the South River, Virginia

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    Historic point source mercury (Hg) contamination from industrial processes on the South River (Waynesboro, Virginia) ended decades ago, but elevated Hg concentrations persist in the river system. In an effort to better understand Hg sources, mobility, and transport in the South River, we analyzed total Hg (THg) concentrations and Hg stable isotope compositions of streambed sediments, stream bank soils, suspended particles, and filtered surface waters. Samples were collected along a longitudinal transect of the South River, starting upstream of the historic Hg contamination point-source and extending downstream to the confluence with the South Fork Shenandoah River. Analysis of the THg concentration and Hg isotopic composition of these environmental samples indicates that the regional background Hg source is isotopically distinct in both Δ<sup>199</sup>Hg and δ<sup>202</sup>Hg from Hg derived from the original source of contamination, allowing the tracing of contamination-sourced Hg throughout the study reach. Three distinct end-members are required to explain the Hg isotopic and concentration variation observed in the South River. A consistent negative offset in δ<sup>202</sup>Hg values (∼0.28‰) was observed between Hg in the suspended particulate and dissolved phases, and this fractionation provides insight into the processes governing partitioning and transport of Hg in this contaminated river system
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