Browsing by Subject "Nutrients"
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Item Open Access A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments.(Nature cell biology, 2024-05) Chidley, Christopher; Darnell, Alicia M; Gaudio, Benjamin L; Lien, Evan C; Barbeau, Anna M; Vander Heiden, Matthew G; Sorger, Peter KBlocking the import of nutrients essential for cancer cell proliferation represents a therapeutic opportunity, but it is unclear which transporters to target. Here we report a CRISPR interference/activation screening platform to systematically interrogate the contribution of nutrient transporters to support cancer cell proliferation in environments ranging from standard culture media to tumours. We applied this platform to identify the transporters of amino acids in leukaemia cells and found that amino acid transport involves high bidirectional flux dependent on the microenvironment composition. While investigating the role of transporters in cystine starved cells, we uncovered a role for serotonin uptake in preventing ferroptosis. Finally, we identified transporters essential for cell proliferation in subcutaneous tumours and found that levels of glucose and amino acids can restrain proliferation in that environment. This study establishes a framework for systematically identifying critical cellular nutrient transporters, characterizing their function and exploring how the tumour microenvironment impacts cancer metabolism.Item Open Access An Analysis of the Total Ecology of Lawn Maintenance in the Chesapeake Bay Watershed(2011-04-28) Junkin, IsabelThe Chesapeake Bay faces a multitude of pressures today from pollution sources, the most pressing being the influx of excessive nutrients. Effluent from waste water treatment plants, animal waste from concentrated animal feeding operations, and agricultural fertilizer are jointly responsible for nutrient loading in the Chesapeake Bay. An often overlooked and even less understood culprit is home lawn fertilization. Of these nutrient contributors, residential turf is the most fragmented and has the largest number of owners, making nutrient inputs from home lawns the most difficult to understand, measure, and regulate. Home lawns from Virginia to upstate New York, from West Virginia to Delaware – 2.85 million acres of green lawns – contribute to the nutrient loading that has so severely degraded the Chesapeake Bay’s waters To better understand all the factors affecting lawn maintenance I take a holistic approach and analyze the total ecology of the issue, including the human, biophysical, and institutional ecologies. First, the human ecology of lawn care is explored to understand the social norms and pressures that determine lawn maintenance behavior. Second, the biophysical ecology of fertilizer nutrients is explored through a literature review. Third, the institutional ecology is defined with a description of the relevant governing bodies and current legal mandates regulating lawn maintenance. This section focuses on a review of the mechanisms used by ten states in recently passed legislation to reduce nutrient pollution from home lawn fertilization. The purpose of this paper is to bring together the human, natural science, management, and policy components of the lawn maintenance issue so as to obtain a comprehensive view of the existing knowledge and structure and of the gaps that need to be filled. The goal of this report is to aid state legislators in understanding the lawn maintenance issue and in refining and passing lawn fertilizer bills similar to those recently enacted by ten states in an effort to reduce nutrient pollution specifically from lawn fertilizers. Lawn fertilizer is only one of many contributing factors degrading water quality, but every reduction of pollution sources, however small, helps to improve the health of the Chesapeake Bay. Strict lawn fertilizer laws regulating lawn maintenance behavior can contribute to the effort to achieve healthier water bodies and a healthier Bay.Item Open Access Evaluating the use of periphyton as an indicator of nutrient over-enrichment in North Carolina wadeable streams(2018-04-26) DiPrete, KatherineThe North Carolina Department of Environmental Quality (NCDEQ) is currently working to define statewide nutrient criteria for its waterbodies. As a subset of this nutrient criteria development project, approaches to identify where high concentrations of nitrogen and phosphorus are occurring in streams were evaluated. The primary focus was to evaluate if biomass and taxonomic identification of periphyton can effectively detect nutrient impacts in wadeable streams. Land use and other water quality parameters were also evaluated as potential tools to predict nutrient concentrations. The goals were to identify preliminary measures that indicate nutrient impairment, to assess if further development of a periphyton monitoring program is feasible, and to make recommendations about the direction of future studies. Results show that high proportions of developed land can be used to identify potential downstream nutrient problem areas. Additionally, high proportions of vegetated land can be used to identify reference stream reaches. Specific conductance is a measurable parameter in the field that can adequately predict elevated concentrations of nitrogen (N) and phosphorus (P). Several results suggested that watershed land-use influences stream periphyton cover and taxonomic composition. Elevated periphyton cover was found downgradient of agricultural land and wastewater treatment plants and an increase in motile species richness was found in periphyton in streams draining watersheds with greater developed land. More research is needed to adequately determine if patterns exist between periphyton biomass, taxonomic composition, and nutrient concentrations.Item Open Access Giardia hinders growth by disrupting nutrient metabolism independent of inflammatory enteropathy.(Nature communications, 2023-05) Giallourou, Natasa; Arnold, Jason; McQuade, Elizabeth T Rogawski; Awoniyi, Muyiwa; Becket, Rose Viguna Thomas; Walsh, Kenneth; Herzog, Jeremy; Gulati, Ajay S; Carroll, Ian M; Montgomery, Stephanie; Quintela, Pedro Henrique; Faust, Angela M; Singer, Steven M; Fodor, Anthony A; Ahmad, Tahmeed; Mahfuz, Mustafa; Mduma, Esto; Walongo, Thomas; Guerrant, Richard L; Balfour Sartor, R; Swann, Jonathan R; Kosek, Margaret N; Bartelt, Luther AGiardia lamblia (Giardia) is among the most common intestinal pathogens in children in low- and middle-income countries (LMICs). Although Giardia associates with early-life linear growth restriction, mechanistic explanations for Giardia-associated growth impairments remain elusive. Unlike other intestinal pathogens associated with constrained linear growth that cause intestinal or systemic inflammation or both, Giardia seldom associates with chronic inflammation in these children. Here we leverage the MAL-ED longitudinal birth cohort and a model of Giardia mono-association in gnotobiotic and immunodeficient mice to propose an alternative pathogenesis of this parasite. In children, Giardia results in linear growth deficits and gut permeability that are dose-dependent and independent of intestinal markers of inflammation. The estimates of these findings vary between children in different MAL-ED sites. In a representative site, where Giardia associates with growth restriction, infected children demonstrate broad amino acid deficiencies, and overproduction of specific phenolic acids, byproducts of intestinal bacterial amino acid metabolism. Gnotobiotic mice require specific nutritional and environmental conditions to recapitulate these findings, and immunodeficient mice confirm a pathway independent of chronic T/B cell inflammation. Taken together, we propose a new paradigm that Giardia-mediated growth faltering is contingent upon a convergence of this intestinal protozoa with nutritional and intestinal bacterial factors.Item Open Access Identifying Pollution Sources for Management Prioritization in the Albemarle-Pamlico Watersheds(2019-04-25) Hillman, IsabelThe Albemarle-Chowan, Roanoke, and Tar-Pamlico watersheds have displayed degradation in water quality in recent history. To address concerns about the effects of poor water quality, the North Carolina Chapter of The Nature Conservancy (TNC) is interested in identifying where nutrients are concentrated across the landscape, and identifying the best management practices (BMP’s) available to address pollutants. To find where pollutant levels are highest, we used InVEST and SPARROW models, and converted raw outputs into hot spots, providing a smaller region for The Nature Conservancy to focus management actions. Within the agriculturally dominated hot spots, we identified 4 best management practices, riparian buffers, cover crops, ditch retention structures, and peatland restoration, as implementation options available to TNC. Scenarios run within InVEST models for each best management practice quantified the scope of action needed and estimated the reduction in nutrient concentrations from implementation. The results of these scenarios showed that TNC will have to address tradeoffs between efficiency and overall impact from best management practices. For example, cover crops were found to be the least efficient at removing nitrogen per acre, but due to the large amount of land available to plant cover crops on, this BMP has the largest potential for reducing nitrogen overall. To aid TNC in finding landowners to approach about using BMP’s, we ran a parcel prioritization, and identified landowners with large parcels containing large amounts of agriculture, peatland, and close to land that is already protected. The results of these analyses will help inform TNC staff as they take steps to improve water quality in the Albemarle-Pamlico region.Item Open Access On the Horizontal Advection and Biogeochemical Impacts of North Atlantic Mode Waters and Boundary Currents(2007-07-26) Palter, Jaime BethUsing a combination of hydrographic data and the trajectories and profiles of isobaric floats, this dissertation evaluates the connections between remote regions in the North Atlantic. First, I establish that the production and advection of the North Atlantic Subtropical Mode Water (STMW) introduces spatial and temporal variability in the subsurface nutrient reservoir of the subtropical gyre. As the mode water is formed, its nutrients are depleted by biological utilization. When the depleted water mass is exported to the gyre, it injects a wedge of low-nutrient water into the upper layers of the ocean. Contrary to intuition, cold winters that promote deep convective mixing and vigorous mode water formation may diminish downstream primary productivity by altering the subsurface delivery of nutrients. Next, the source of elevated nutrient concentrations in the Gulf Stream is assessed. The historical hydrographic data suggest that imported water advected into the Gulf Stream via the tropics supplies an important source of nutrients to the Gulf Stream. Because the high nutrients are likely imported from the tropics, diapycnal mixing need not be invoked to explain the Gulf Stream's high nutrient concentrations, as had been previously hypothesized. Furthermore, nutrients do not increase along the length of the Stream, as would be expected with strong diapycnal mixing.Finally, profiling float data are used to investigate how the Labrador Sea Water enters the Deep Western Boundary Current, one of the primary pathways by which it exits the subpolar gyre. With the trajectories and profiles of an extensive array of P-ALACE floats I evaluate three processes for their role in the entry of Labrador Sea Water in the Deep Western Boundary Current (DWBC): 1) LSW is formed directly in the DWBC, 2) Eddies flux LSW laterally from the interior Labrador Sea to the DWBC, and 3) A horizontally divergent mean flow advects LSW from the interior to the DWBC. Each of the three processes has the potential to remove heat from the boundary current, and both the formation of LSW directly in the boundary current and the eddy heat flux are possible sources of interannual variability in the exported LSW product.Item Open Access Redefining algal bloom management pathways in North Carolina(2020-04-23) Greif, Jake; Roth, Lindsay; Swann, Kristine; Townsend, Tristen; Watson, CarolineAlgal blooms are a common occurrence in North Carolina lakes and reservoirs, and recent data suggests they are occurring more frequently. Due to environmental, health, and economic impacts of these occurrences, the North Carolina Department of Environmental Quality (NCDEQ) is invested in understanding the trends in drivers of harmful algal blooms. This project analyzes Ambient Lake Monitoring Data sourced from the Division of Water Resources within NCDEQ to assess potential strategies for both identifying harmful algal blooms and managing the overall occurrences of algal blooms for North Carolina lakes and reservoirs. Our objectives were to: 1) define reference conditions in lakes and reservoirs in North Carolina, 2) predict waterbodies most at risk of algal blooms based on physical and spatial factors, 3) analyze and make recommendations for phytoplankton thresholds, 4) determine temporal trends in blooms, and 5) compare North Carolina water quality criteria the with nationwide policy landscape. Reference conditions were estimated by taking the median value of monthly 25th percentiles from the most sampled months (May – September) for chemical and biological data. Relative to other ecoregions, the Piedmont’s reference values were consistently high for chemical and biological data; further, the reference conditions for phytoplankton metrics in the Piedmont often exceed current bloom and dominance criteria set by NCDEQ, suggesting it is typical for the Piedmont to experience algal blooms even under the best circumstances. Principal component and redundancy analyses were also performed to assess the relationships among phytoplankton and environmental variables. Results show cyanobacteria vary differently than most other algal groups and are highly associated with chlorophyll-a and nutrients. In order to determine the physical and spatial drivers that make waterbodies vulnerable to algal blooms, we created linear models to predict algal bloom indicators from physical and land use characteristics. Our results suggest that the most vulnerable systems are small reservoirs with dense stream networks that are surrounded by land uses producing high nutrient loads. These findings highlight potential avenues for improved bloom management, such as updating inconsistent bloom criteria and increasing monitoring of at-risk waterbodies. Future studies may incorporate additional physical and spatial characteristics such as precipitation, finer resolution watershed data, and more detailed data about reservoirs including residence time, reservoir order, and reservoir age. Bloom criteria were assessed by calculating the percent of samples which would be classified as potentially harmful algal blooms based on NCDEQ criteria. Unit density and biovolume metrics were found to classify samples across the state inconsistently, with 53.4% and 14.6% in exceedance, respectively. Additionally, sample data were compared to World Health Organization (WHO) guidelines for safe recreational waters using the metric of cyanobacteria cell density. Based on WHO guidelines, 78.3% of samples would be considered at least a moderate risk to human health and 54.6% would be considered a high risk. These results suggest NCDEQ may benefit from updating current bloom criteria to classify samples more consistently; furthermore, the inclusion of cyanobacteria cell density as a metric may allow NCDEQ to have assessments more comparable to international guidelines. Algal temporal trends were analyzed by running a mixed model with year as a fixed effect and waterbody as a random effect to account for temporal inconsistency in monitoring efforts. Chlorophyll-a was found to increase by 1.4 µg/L per year in May and decrease by 1.3 µg/L per year in September. Cyanobacterial relative abundance was found to increase by 1% per year in May and August, and 2% per year in June and September. Our results indicate a seasonal shift in algal blooms, occurring earlier in the year, and an increase in cyanobacteria dominance, which could lead to an increase in toxins being produced in waterbodies. Administrative codes for 47 states were assessed for nutrient criteria standards and associated sub-sectioning trends (site-specific, statewide, ecoregional, hydromorphic, designated use) and water quality parameters (chlorophyll-a, total nitrogen, total phosphorus, clarity). Nationally, it is common for states to subsection nutrient criteria in multiple ways to apply criteria to narrowed conditions. Most states have multiple water quality parameters used within criteria. These trends were further broken down by North Carolina ecoregions to find the ranges in nutrient criteria values used in bordering states that share ecoregions in common with North Carolina. North Carolina’s existing nutrient criteria for chlorophyll-a fall approximately midway within these ecoregional ranges, and as NCDEQ moves forward with revising nutrient criteria for lakes and reservoirs, these ecoregional ranges can be used as a reference. NCDEQ is revising nutrient criteria for lakes and reservoirs at a site-specific scale presently, and while this may be the most efficient method of setting the criteria, other options of sub-sectioning could be useful including sub-sectioning based on ecoregion or physical characteristics. Further modeling of chlorophyll-a by ecoregion or physical attribute are needed to assess these options. Based on our results, potential management improvements that NCDEQ could implement include changing water monitoring schedules, updating bloom criteria, and prioritizing lake monitoring based on certain physical and spatial characteristics. Additionally, NCDEQ may benefit from further investigating what drivers contribute to increasing algal blooms and cyanobacteria dominance, and how those drivers concurrently change with a changing climate.