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  1. Abstract

    The cycling of marine particulate matter is critical for sequestering carbon in the deep ocean and in marine sediments. Biogenic minerals such as calcium carbonate (CaCO3) and opal add density to more buoyant organic material, facilitating particle sinking and export. Here, we compile and analyze a global data set of particulate organic carbon (POC), particulate inorganic carbon (PIC, or CaCO3), and biogenic silica (bSi, or opal) concentrations collected using large volume pumps (LVPs). We analyze the distribution of all three biogenic phases in the small (1–53 μm) and large (>53 μm) size classes. Over the entire water column 76% of POC exists in the small size fraction. Similarly, the small size class contains 82% of PIC, indicating the importance of small‐sized coccolithophores to the PIC budget of the ocean. In contrast, 50% of bSi exists in the large size fraction, reflecting the larger size of diatoms and radiolarians compared with coccolithophores. We use PIC:POC and bSi:POC ratios in the upper ocean to document a consistent signal of shallow mineral dissolution, likely linked to biologically mediated processes. Sediment trap PIC:POC and bSi:POC are elevated with respect to LVP samples and increase strongly with depth, indicating the concentration of mineral phases and/or a deficit of POC in large sinking particles. We suggest that future sampling campaigns pair LVPs with sediment traps to capture the full particulate field, especially the large aggregates that contribute to mineral‐rich deep ocean fluxes, and may be missed by LVPs.

     
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  2. We have developed a non-cationic transfection vector in the form of bottlebrush polymer-antisense oligonucleotide (ASO) conjugates. Termed pacDNA (polymer-assisted compaction of DNA), these agents show improved biopharmaceutical characteristics and antisense potency in vivo while suppressing non-antisense side effects. Nonetheless, there still is a lack of the mechanistic understanding of the cellular uptake, subcellular trafficking, and gene knockdown with pacDNA. Here, we show that the pacDNA enters human non-small cell lung cancer cells (NCI-H358) predominantly by scavenger receptor-mediated endocytosis and macropinocytosis and trafficks via the endolysosomal pathway within the cell. The pacDNA significantly reduces a target gene expression (KRAS) in the protein level but not in the mRNA level, despite that the transfection of certain free ASOs causes ribonuclease H1 (RNase H)-dependent degradation of KRAS mRNA. In addition, the antisense activity of pacDNA is independent of ASO chemical modification, suggesting that the pacDNA always functions as a steric blocker. 
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  3. The mutant form of the guanosine triphosphatase (GTPase) KRAS is a key driver in human tumors but remains a challenging therapeutic target, making KRAS MUT cancers a highly unmet clinical need. Here, we report a class of bottlebrush polyethylene glycol (PEG)–conjugated antisense oligonucleotides (ASOs) for potent in vivo KRAS depletion. Owing to their highly branched architecture, these molecular nanoconstructs suppress nearly all side effects associated with DNA–protein interactions and substantially enhance the pharmacological properties of the ASO, such as plasma pharmacokinetics and tumor uptake. Systemic delivery to mice bearing human non–small-cell lung carcinoma xenografts results in a significant reduction in both KRAS levels and tumor growth, and the antitumor performance well exceeds that of current popular ASO paradigms, such as chemically modified oligonucleotides and PEGylation using linear or slightly branched PEG. Importantly, these conjugates relax the requirement on the ASO chemistry, allowing unmodified, natural phosphodiester ASOs to achieve efficacy comparable to that of chemically modified ones. Both the bottlebrush polymer and its ASO conjugates appear to be safe and well tolerated in mice. Together, these data indicate that the molecular brush–ASO conjugate is a promising therapeutic platform for the treatment of KRAS -driven human cancers and warrant further preclinical and clinical development. 
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  4. Abstract

    Ocean alkalinity plays a fundamental role in the apportionment of CO2between the atmosphere and the ocean. The primary driver of the ocean's vertical alkalinity distribution is the formation of calcium carbonate (CaCO3) by organisms at the ocean surface and its dissolution at depth. This so‐called “CaCO3counterpump” is poorly constrained, however, both in terms of how much CaCO3is exported from the surface ocean, and at what depth it dissolves. Here, we created a steady‐state model of global ocean alkalinity using Ocean Circulation Inverse Model transport, biogeochemical cycling, and field‐tested calcite and aragonite dissolution kinetics. We find that limiting CaCO3dissolution to below the aragonite and calcite saturation horizons cannot explain excess alkalinity in the upper ocean, and that models allowing dissolution above the saturation horizons best match observations. Linking dissolution to organic matter respiration, or imposing a constant dissolution rate both produce good model fits. Our best performing models require export between 1.1 and 1.8 Gt PIC y−1(from 73 m), but all converge to 1.0 Gt PIC y−1export at 279 m, indicating that both high‐ and low‐export scenarios can match observations, as long as high export is coupled to high dissolution in the upper ocean. These results demonstrate that dissolution is not a simple function of seawater CaCO3saturation (Ω) and calcite or aragonite solubility, and that other mechanisms, likely related to the biology and ecology of calcifiers, must drive significant dissolution throughout the water column.

     
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  5. Abstract

    We have designed, built, tested, and deployed a novel device to extract porewater from deep‐sea sediments in situ, constructed to work with a standard multicorer. Despite the importance of porewater measurements for numerous applications, many sampling artifacts can bias data and interpretation during traditional porewater processing from shipboard‐processed cores. A well‐documented artifact occurs in deep‐sea porewater when carbonate precipitates during core recovery as a function of temperature and pressure changes, while porewater is in contact with sediment grains before filtration, thereby lowering porewater alkalinity and dissolved inorganic carbon (DIC). Here, we present a novel device built to obviate these sampling artifacts by filtering porewater in situ on the seafloor, with a focus near the sediment–water interface on cm‐scale resolution, to obtain accurate porewater profiles. We document 1–10% alkalinity loss in shipboard‐processed sediment cores compared to porewater filtered in situ, at depths of 1600–3200 m. We also show that alkalinity loss is a function of both weight % sedimentary CaCO3and water column depth. The average ratio of alkalinity loss to DIC loss in shipboard‐processed sediment cores relative to in situ porewater is 2.2, consistent with the signal expected from carbonate precipitation. In addition to collecting porewater for defining natural profiles, we also conducted the first in situ dissolution experiments within the sediment column using isotopically labeled calcite. We present evidence of successful deployments of this device on and adjacent to the Cocos Ridge in the Eastern Equatorial Pacific across a range of depths and calcite saturation states.

     
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  6. null (Ed.)
    The dissolution of CaCO 3 minerals in the ocean is a fundamental part of the marine alkalinity and carbon cycles. While there have been decades of work aimed at deriving the relationship between dissolution rate and mineral saturation state (a so-called rate law), no real consensus has been reached. There are disagreements between laboratory- and field-based studies and differences in rates for inorganic and biogenic materials. Rates based on measurements on suspended particles do not always agree with rates inferred from measurements made near the sediment–water interface of the actual ocean. By contrast, the freshwater dissolution rate of calcite has been well described by bulk rate measurements from a number of different laboratories, fit by basic kinetic theory, and well studied by atomic force microscopy and vertical scanning interferometry to document the processes at the atomic scale. In this review, we try to better unify our understanding of carbonate dissolution in the ocean via a relatively new, highly sensitive method we have developed combined with a theoretical framework guided by the success of the freshwater studies. We show that empirical curve fits of seawater data as a function of saturation state do not agree, largely because the curvature is itself a function of the thermodynamics. Instead, we show that models that consider both surface energetic theory and the complicated speciation of seawater and calcite surfaces in seawater are able to explain most of the most recent data.This new framework can also explain features of the historical data that have not been previously explained. The existence of a kink in the relationship between rate and saturation state, reflecting a change in dissolution mechanism, may be playing an important role in accelerating CaCO 3 dissolution in key sedimentary environments. 
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