Most cells in the body acquire iron via receptor-mediated endocytosis of transferrin, the circulating iron transport protein. When cellular iron levels are sufficient, the uptake of transferrin ...decreases to limit further iron assimilation and prevent excessive iron accumulation. In iron overload conditions, such as hereditary hemochromatosis and thalassemia major, unregulated iron entry into the plasma overwhelms the carrying capacity of transferrin, resulting in non-transferrin-bound iron (NTBI), a redox-active, potentially toxic form of iron. Plasma NTBI is rapidly cleared from the circulation primarily by the liver and other organs (e.g., pancreas, heart, and pituitary) where it contributes significantly to tissue iron overload and related pathology. While NTBI is usually not detectable in the plasma of healthy individuals, it does appear to be a normal constituent of brain interstitial fluid and therefore likely serves as an important source of iron for most cell types in the CNS. A growing body of literature indicates that NTBI uptake is mediated by non-transferrin-bound iron transporters such as ZIP14, L-type and T-type calcium channels, DMT1, ZIP8, and TRPC6. This review provides an overview of NTBI uptake by various tissues and cells and summarizes the evidence for and against the roles of individual transporters in this process.
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•Non-transferrin-bound iron (NTBI) appears in the plasma in iron overload.•NTBI is a major contributor to pathological iron loading of various tissues.•Tissue uptake of NTBI is mediated by plasma membrane transporters.•NTBI transporters include ZIP14, LTCCs, TTCCs, DMT1, ZIP8, and TRPC6.•NTBI transporters function in a cell-type and tissue-specific manner.
Cellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and ...out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.
Systemic insecticides are applied to plants using a wide variety of methods, ranging from foliar sprays to seed treatments and soil drenches. Neonicotinoids and fipronil are among the most widely ...used pesticides in the world. Their popularity is largely due to their high toxicity to invertebrates, the ease and flexibility with which they can be applied, their long persistence, and their systemic nature, which ensures that they spread to all parts of the target crop. However, these properties also increase the probability of environmental contamination and exposure of nontarget organisms. Environmental contamination occurs via a number of routes including dust generated during drilling of dressed seeds, contamination and accumulation in arable soils and soil water, runoff into waterways, and uptake of pesticides by nontarget plants via their roots or dust deposition on leaves. Persistence in soils, waterways, and nontarget plants is variable but can be prolonged; for example, the half-lives of neonicotinoids in soils can exceed 1,000 days, so they can accumulate when used repeatedly. Similarly, they can persist in woody plants for periods exceeding 1 year. Breakdown results in toxic metabolites, though concentrations of these in the environment are rarely measured. Overall, there is strong evidence that soils, waterways, and plants in agricultural environments and neighboring areas are contaminated with variable levels of neonicotinoids or fipronil mixtures and their metabolites (soil, parts per billion (ppb)-parts per million (ppm) range; water, parts per trillion (ppt)-ppb range; and plants, ppb-ppm range). This provides multiple routes for chronic (and acute in some cases) exposure of nontarget animals. For example, pollinators are exposed through direct contact with dust during drilling; consumption of pollen, nectar, or guttation drops from seed-treated crops, water, and consumption of contaminated pollen and nectar from wild flowers and trees growing near-treated crops. Studies of food stores in honeybee colonies from across the globe demonstrate that colonies are routinely and chronically exposed to neonicotinoids, fipronil, and their metabolites (generally in the 1–100 ppb range), mixed with other pesticides some of which are known to act synergistically with neonicotinoids. Other nontarget organisms, particularly those inhabiting soils, aquatic habitats, or herbivorous insects feeding on noncrop plants in farmland, will also inevitably receive exposure, although data are generally lacking for these groups. We summarize the current state of knowledge regarding the environmental fate of these compounds by outlining what is known about the chemical properties of these compounds, and placing these properties in the context of modern agricultural practices.
The Sthenurinae were a diverse subfamily of short-faced kangaroos that arose in the Miocene and diversified during the Pliocene and Pleistocene. Many species possessed skull morphologies that were ...relatively structurally reinforced with bone, suggesting that they were adapted to incorporate particularly resistant foods into their diets. However, the functional roles of many unique, robust features of the sthenurine cranium are not yet clearly defined. Here, the finite element method is applied to conduct a comprehensive analysis of unilateral biting along the cheek tooth battery of a well-represented sthenurine, Simosthenurus occidentalis. The results are compared with those of an extant species considered to be of most similar ecology and cranial proportions to this species, the koala (Phascolarctos cinereus). The simulations reveal that the cranium of S. occidentalis could produce and withstand comparatively high forces during unilateral biting. Its greatly expanded zygomatic arches potentially housed enlarged zygomaticomandibularis muscles, shown here to reduce the risk of dislocation of the temporomandibular joint during biting with the rear of a broad, extensive cheek tooth row. This may also be a function of the zygomaticomandibularis in the giant panda (Ailuropoda melanoleuca), another species known to exhibit an enlarged zygomatic arch and hypertrophy of this muscle. Furthermore, the expanded frontal plates of the S. occidentalis cranium form broad arches of bone with the braincase and deepened maxillae that each extend from the anterior tooth rows to their opposing jaw joints. These arches are demonstrated here to be a key feature in resisting high torsional forces during unilateral premolar biting on large, resistant food items. This supports the notion that S. occidentalis fed thick, lignified vegetation directly to the cheek teeth in a similar manner to that described for the giant panda when crushing mature bamboo culms.
CoastSat is an open-source software toolkit written in Python that enables the user to obtain time-series of shoreline position at any sandy coastline worldwide from 30+ years (and growing) of ...publicly available satellite imagery. The toolkit exploits the capabilities of Google Earth Engine to efficiently retrieve Landsat and Sentinel-2 images cropped to any user-defined region of interest. The resulting images are pre-processed to remove cloudy pixels and enhance spatial resolution, before applying a robust and generic shoreline detection algorithm. This novel shoreline detection technique combines a supervised image classification and a sub-pixel resolution border segmentation to map the position of the shoreline with an accuracy of ~10 m. The purpose of CoastSat is to provide coastal managers, engineers and scientists a user-friendly and practical toolkit to monitor and explore their coastlines. The software is freely-available on GitHub (https://github.com/kvos/CoastSat) and is accompanied by guided examples (Jupyter Notebook) plus step-by-step README documentation.
•Global shoreline mapping toolbox from publicly available Landsat and Sentinel-2 satellite imagery.•Open-source Python toolkit that enables users to obtain 30+ years of satellite-derived shorelines at any beach worldwide.•Satellite images of the user-defined region of interest are retrieved efficiently with Google Earth Engine.•The sand/water interface is automatically mapped using a robust sub-pixel resolution shoreline detection technique.
The ongoing expansion of shrub cover in response to climate change represents a unique opportunity to explore the link between soil microbial communities and vegetation changes. This link is ...particularly important in peatlands where shrub expansion is expected to feed back negatively on the carbon sink capacity of these ecosystems. Microbial community structure and function were measured seasonally in four peatlands located along an altitude gradient representing a natural gradient of climate and associated vascular plant abundance. We show that increased soil temperature and reduced water content are associated with greater vascular plant biomass, in particular that of ericoids, and that this, in turn, is correlated with greater microbial biomass. More specifically, microbial community structure is characterized by an increasing dominance of fungi over bacteria with improved soil oxygenation. We also found that the carbon and nitrogen stoichiometry of microbial biomass differs in relation to soil microbial community structure and that this is ultimately associated with a different investment in extracellular enzymatic activity. Our findings highlight the fact that the determination of the structural identity of microbial communities can help to explain the biogeochemical dynamics of organic matter and provide a better understanding of ecosystem response to environmental changes.
This study uses the Wabash National Study on Liberal Arts Education to understand student study abroad participation while holding a student's prior intent to study abroad constant. The study ...augments previous use of the data set by (1) holding intent to study abroad constant across models and (2) focusing on study abroad participation and the socioeconomic construct of parental education. Consistent with theories of high-brow embodied cultural capital and effectively maintained inequality, students of advanced degree parents are more likely to study abroad after holding intent to study abroad and the various forms of capital constant. Intent to study abroad, gender, prior and current academic characteristics, university type, diverse coursework, orientation towards diversity, non-classroom faculty interactions, and co-curricular involvement have associations with study abroad participation. After controlling for intent to study abroad, individual analyses of student socioeconomic status indicate that intent to participate, academic achievement, and liberal arts institution attendance remain salient for increasing study abroad participation, and some other factors had heterogeneous associations among subgroups.
Nearly all forms of hereditary hemochromatosis are characterized by pathological iron accumulation in the liver, pancreas, and heart. These tissues preferentially load iron because they take up ...non-transferrin-bound iron (NTBI), which appears in the plasma during iron overload. Yet, how tissues take up NTBI is largely unknown. We report that ablation of Slc39a14, the gene coding for solute carrier SLC39A14 (also called ZIP14), in mice markedly reduced the uptake of plasma NTBI by the liver and pancreas. To test the role of SLC39A14 in tissue iron loading, we crossed Slc39a14−/− mice with Hfe−/− and Hfe2−/− mice, animal models of type 1 and type 2 (juvenile) hemochromatosis, respectively. Slc39a14 deficiency in hemochromatotic mice greatly diminished iron loading of the liver and prevented iron deposition in hepatocytes and pancreatic acinar cells. The data suggest that inhibition of SLC39A14 may mitigate hepatic and pancreatic iron loading and associated pathologies in iron overload disorders.
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•SLC39A14 mediates non-transferrin-bound iron uptake by the liver and pancreas•SLC39A14 is required for Hfe−/− and Hfe2−/− mice to develop hepatic iron overload•SLC39A14 is required for iron loading of hepatocytes and pancreatic acinar cells•SLC39A14 represents a possible therapeutic target for mitigating tissue iron loading
Plasma non-transferrin-bound iron (NTBI) is a main contributor to tissue iron loading in iron overload disorders such as hereditary hemochromatosis. Jenkitkasemwong et al. show that loss of the metal-ion transporter SLC39A14 impairs NTBI uptake by the liver and prevents hepatic iron overload in mouse models of hemochromatosis.
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