Soil health: A common focus for one health and planetary health interventions.

Proponents of both the One Health and Planetary Health paradigms have acknowledged that current methods of agricultural food production are driving many environmental changes with negative human health consequences, including climate change, deforestation, and the emergence of zoonotic disease and antimicrobial resistance. Currently, the training of human health, veterinary, and public health professionals typically does not include aspects of soil health. Much of the resultant discussion in One Health and Planetary Health circles regarding interventions to address the health impact of agricultural practices has focused on measures such as advocating for dietary change toward plant based diets and increasing food safety, biosecurity, disease surveillance and antimicrobial stewardship. A greater understanding of soil health and its relationship to agricultural practices could prove foundational to many of the problems that the One Health and Planetary Health perspectives aim to address, including antimicrobial resistance, zoonotic disease emergence, food security, and climate change. A consequent global focus on the health of soils offers a promise of specific opportunities for preventive interventions and a greater convergence between the One Health and Planetary Health approaches.

Interspecies Differences in 6PPD-Quinone Toxicity Across Seven Fish Species: Metabolite Identification and Semiquantification.

N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire antidegradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations that surpass those measured in the environment. The reasons for these marked differences in sensitivity are presently unknown. The objective of this research was to explore potential toxicokinetic drivers of species sensitivity by characterizing biliary metabolites of 6PPD-Q in sensitive and tolerant fishes. For the first time, we identified an O-glucuronide metabolite of 6PPD-Q using high-resolution mass spectrometry. The semiquantified levels of this metabolite in tolerant species or life stages, including white sturgeon (Acipenser transmontanus), chinook salmon (Oncorhynchus tshawytscha), westslope cutthroat trout (Oncorhynchus clarkii lewisi), and nonfry life stages of Atlantic salmon (Salmo salar), were greater than those in sensitive species, including coho salmon (Oncorhynchus kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting that tolerant species might detoxify 6PPD-Q more effectively. Thus, we hypothesize that differences in species sensitivity are a result of differences in basal expression of biotransformation enzyme across various fish species. Moreover, the semiquantification of 6PPD-Q metabolites in bile extracted from wild-caught fish might be a useful biomarker of exposure to 6PPD-Q, thereby being valuable to environmental monitoring and risk assessment.

Trends in soil organic matter and topsoil thickness under regenerative practices at the University of Washington student farm.

Conventional methods of agriculture, especially tillage, are often accompanied by soil degradation in the form of erosion and organic matter depletion. Regenerative agricultural methods seek to repair soil ecosystems by building topsoil and soil organic matter (SOM), decreasing reliance on chemical fertilizers and increasing both water retention capacity and the diversity and quantity of soil microbial and fungal communities. The University of Washington (UW) student farm is an organic and regeneratively managed site on the UW Seattle campus. Over the past 20 years the farm gradually expanded so locations on the farm encompass both unimproved topsoil and soils managed regeneratively for periods of 5 to 20 years. This arrangement allows a time-trend analysis of soil development under regenerative methods. Measurements of topsoil thickness (defined as the distance from the ground surface to the base of the soil A horizon) and organic matter content were collected across 14 distinct plots on the farm to quantify trends over time and estimate net change in SOM (and soil organic carbon, or SOC). While SOM content weakly increased by 0.5% per year, topsoil thickness exhibited a significant linear increase of 0.86 cm per year. Over a twenty-year period under the management practices of the UW Farm total organic carbon storage in soils, determined using topsoil thickness, density, and SOC content, increased by between 4 and 14 t ha-1 yr-1. The general increases in topsoil thickness, SOM content, and total soil carbon demonstrate the potential of soil-health-focused practices to help maintain a productive and efficient urban growing space.

clotFoam: An open-source framework to simulate blood clot formation under arterial flow.

Blood clotting involves the coupled processes of platelet aggregation and coagulation. Simulating clotting under flow in complex geometries is challenging due to multiple temporal and spatial scales and high computational cost. clotFoam is an open-source software developed in OpenFOAM that employs a continuum model of platelet advection, diffusion, and aggregation in a dynamic fluid environment and a simplified coagulation model with proteins that advect, diffuse, and react within the fluid and with wall-bound species through reactive boundary conditions. Our framework provides the foundation on which one can build more complex models and perform reliable simulations in almost any computational domain.

Spatial ecology and conservation of leatherback turtles (Dermochelys coriacea) nesting in Bioko, Equatorial Guinea.

Bioko Island (Equatorial Guinea) hosts important nesting habitat for leatherback sea turtles, with the main nesting beaches found on the island's southern end. Nest monitoring and protection have been ongoing for more than two decades, although distribution and habitat range at sea remains to be determined. This study uses satellite telemetry to describe the movements of female leatherback turtles (n = 10) during and following the breeding season, tracking them to presumed offshore foraging habitats in the south Atlantic Ocean. Leatherback turtles spent 100% of their time during the breeding period within the Exclusive Economic Zone (EEZ) of Equatorial Guinea, with a core distribution focused on the south of Bioko Island extending up to 10 km from the coast. During this period, turtles spent less than 10% of time within the existing protected area. Extending the border of this area by 3 km offshore would lead to a greater than threefold increase in coverage of turtle distribution (29.8 ± 19.0% of time), while an expansion to 15 km offshore would provide spatial coverage for more than 50% of tracking time. Post-nesting movements traversed the territorial waters of Sao Tome and Principe (6.4%of tracking time), Brazil (0.85%), Ascension (1.8%), and Saint Helena (0.75%). The majority (70%) of tracking time was spent in areas beyond national jurisdiction (i.e. the High Seas). This study reveals that conservation benefits could be achieved by expanding existing protected areas stretching from the Bioko coastal zone, and suggests shared migratory routes and foraging space between the Bioko population and other leatherback turtle rookeries in this region.

A comparison of past and present computational methods for shape analysis of double-shell x-ray radiographs.

Implosion symmetry is a key requirement in achieving a robust burning plasma in inertial confinement fusion experiments. In double-shell capsule implosions, we are interested in the shape of the inner shell as it pushes on the fuel. Shape analysis is a popular technique for studying said symmetry during implosion. Combinations of filtering and contour-finding algorithms are studied for their promise in reliably recovering Legendre shape coefficients from synthetic radiographs of double-shell capsules with applied levels of noise. A radial lineout max(slope) method when used on an image pre-filtered with non-local means and a variant of the marching squares algorithm are able to recover p0, p2, and p4 maxslope Legendre shape coefficients with mean pixel discrepancy errors of 2.81 and 3.06, respectively, for the noisy synthetic radiographs we consider. This improves upon prior radial lineout methods paired with Gaussian filtering, which we show to be unreliable and whose performance is dependent on input parameters that are difficult to estimate.

clotFoam: An Open-Source Framework to Simulate Blood Clot Formation Under Arterial Flow.

Blood clotting involves the coupled processes of platelet aggregation and coagulation. Simulating clotting under flow in complex geometries is challenging due to multiple temporal and spatial scales and high computational cost. clotFoam is an open-source software developed in OpenFOAM that employs a continuum model of platelet advection, diffusion, and aggregation in a dynamic fluid environment and a simplified coagulation model with proteins that advect, diffuse, and react within the fluid and with wall-bound species through reactive boundary conditions. Our framework provides the foundation on which one can build more complex models and perform reliable simulations in almost any computational domain.

Invited article: X-ray phase contrast imaging in inertial confinement fusion and high energy density research.

X-ray phase contrast imaging (XPCI) provides enhanced image contrast beyond absorption-based x-ray imaging alone due to refraction and diffraction from gradients in the object material density. It is sensitive to small variations in density, such as internal voids, cracks, grains, defects, and material flow, as well as to stronger density variations such as from a shock wave. Beyond its initial use in biology and materials science, XPCI is now routinely used in inertial confinement fusion (ICF) and high energy density (HED) research, first to characterize ICF capsules and targets, and later applied in dynamic experiments, where coherent x-ray sources, ultrafast x-ray pulses, and high temporal and spatial resolution are required. In this Review article, XPCI image formation theory is presented, its diverse use in ICF and HED research is discussed, the unique requirements for ultrafast XPCI imaging are given, as well as current challenges and issues in its use.

Novel fabrication tools for dynamic compression targets with engineered voids using photolithography methods.

Mesoscale imperfections, such as pores and voids, can strongly modify the properties and the mechanical response of materials under extreme conditions. Tracking the material response and microstructure evolution during void collapse is crucial for understanding its performance. In particular, imperfections in the ablator materials, such as voids, can limit the efficiency of the fusion reaction and ultimately hinder ignition. To characterize how voids influence the response of materials during dynamic loading and seed hydrodynamic instabilities, we have developed a tailored fabrication procedure for designer targets with voids at specific locations. Our procedure uses SU-8 as a proxy for the ablator materials and hollow silica microspheres as a proxy for voids and pores. By using photolithography to design the targets' geometry, we demonstrate precise and highly reproducible placement of a single void within the sample, which is key for a detailed understanding of its behavior under shock compression. This fabrication technique will benefit high-repetition rate experiments at x-ray and laser facilities. Insight from shock compression experiments will provide benchmarks for the next generation of microphysics modeling.

Multi-frame, ultrafast, x-ray microscope for imaging shockwave dynamics.

Inertial confinement fusion (ICF) holds increasing promise as a potential source of abundant, clean energy, but has been impeded by defects such as micro-voids in the ablator layer of the fuel capsules. It is critical to understand how these micro-voids interact with the laser-driven shock waves that compress the fuel pellet. At the Matter in Extreme Conditions (MEC) instrument at the Linac Coherent Light Source (LCLS), we utilized an x-ray pulse train with ns separation, an x-ray microscope, and an ultrafast x-ray imaging (UXI) detector to image shock wave interactions with micro-voids. To minimize the high- and low-frequency variations of the captured images, we incorporated principal component analysis (PCA) and image alignment for flat-field correction. After applying these techniques we generated phase and attenuation maps from a 2D hydrodynamic radiation code (xRAGE), which were used to simulate XPCI images that we qualitatively compare with experimental images, providing a one-to-one comparison for benchmarking material performance. Moreover, we implement a transport-of-intensity (TIE) based method to obtain the average projected mass density (areal density) of our experimental images, yielding insight into how defect-bearing ablator materials alter microstructural feature evolution, material compression, and shock wave propagation on ICF-relevant time scales.

Soil health and nutrient density: preliminary comparison of regenerative and conventional farming.

Several independent comparisons indicate regenerative farming practices enhance the nutritional profiles of crops and livestock. Measurements from paired farms across the United States indicate differences in soil health and crop nutrient density between fields worked with conventional (synthetically-fertilized and herbicide-treated) or regenerative practices for 5 to 10 years. Specifically, regenerative farms that combined no-till, cover crops, and diverse rotations-a system known as Conservation Agriculture-produced crops with higher soil organic matter levels, soil health scores, and levels of certain vitamins, minerals, and phytochemicals. In addition, crops from two regenerative no-till vegetable farms, one in California and the other in Connecticut, had higher levels of phytochemicals than values reported previously from New York supermarkets. Moreover, a comparison of wheat from adjacent regenerative and conventional no-till fields in northern Oregon found a higher density of mineral micronutrients in the regenerative crop. Finally, a comparison of the unsaturated fatty acid profile of beef and pork raised on one of the regenerative farms to a regional health-promoting brand and conventional meat from local supermarkets, found higher levels of omega-3 fats and a more health-beneficial ratio of omega-6 to omega-3 fats. Despite small sample sizes, all three crop comparisons show differences in micronutrient and phytochemical concentrations that suggest soil health is an under appreciated influence on nutrient density, particularly for phytochemicals not conventionally considered nutrients but nonetheless relevant to chronic disease prevention. Likewise, regenerative grazing practices produced meat with a better fatty acid profile than conventional and regional health-promoting brands. Together these comparisons offer preliminary support for the conclusion that regenerative soil-building farming practices can enhance the nutritional profile of conventionally grown plant and animal foods.

Remodelin Is a Cryptic Assay Interference Chemotype That Does Not Inhibit NAT10-Dependent Cytidine Acetylation.

Remodelin is a putative small molecule inhibitor of the RNA acetyltransferase NAT10 which has shown preclinical efficacy in models of the premature aging disease Hutchinson-Gilford Progeria Syndrome (HGPS). Here we evaluate remodelin's assay interference characteristics and effects on NAT10-catalyzed RNA cytidine acetylation. We find the remodelin chemotype constitutes a cryptic assay interference compound, which does not react with small molecule thiols but demonstrates protein reactivity in ALARM NMR and proteome-wide affinity profiling assays. Biophysical analyses find no direct evidence for interaction of remodelin with the NAT10 acetyltransferase active site. Cellular studies verify that N4-acetylcytidine (ac4C) is a nonredundant target of NAT10 activity in human cell lines and find that this RNA modification is not affected by remodelin treatment in several orthogonal assays. These studies display the potential for remodelin's chemotype to interact with multiple protein targets in cells and indicate remodelin should not be applied as a specific chemical inhibitor of NAT10-catalyzed RNA acetylation.

Neural network for 3D inertial confinement fusion shell reconstruction from single radiographs.

In inertial confinement fusion (ICF), x-ray radiography is a critical diagnostic for measuring implosion dynamics, which contain rich three-dimensional (3D) information. Traditional methods for reconstructing 3D volumes from 2D radiographs, such as filtered backprojection, require radiographs from at least two different angles or lines of sight (LOS). In ICF experiments, the space for diagnostics is limited, and cameras that can operate on fast timescales are expensive to implement, limiting the number of projections that can be acquired. To improve the imaging quality as a result of this limitation, convolutional neural networks (CNNs) have recently been shown to be capable of producing 3D models from visible light images or medical x-ray images rendered by volumetric computed tomography. We propose a CNN to reconstruct 3D ICF spherical shells from single radiographs. We also examine the sensitivity of the 3D reconstruction to different illumination models using preprocessing techniques such as pseudo-flatfielding. To resolve the issue of the lack of 3D supervision, we show that training the CNN utilizing synthetic radiographs produced by known simulation methods allows for reconstruction of experimental data as long as the experimental data are similar to the synthetic data. We also show that the CNN allows for 3D reconstruction of shells that possess low mode asymmetries. Further comparisons of the 3D reconstructions with direct multiple LOS measurements are justified.

Comparison of cellooligosaccharide conformations in complexes with proteins with energy maps for cellobiose.

Shapes (conformations) of cellulose molecules are described by their glycosidic linkage torsion angles ϕ and ψ. Although the torsions are known for cellulose in crystals, amorphous shapes are also interesting for understanding reactivity and physical properties. ϕ and ψ determination for unorganized matter is difficult; one approach is to study their range in many related molecules. For example, linkage torsions of cellulose should be similar to those in cellobiose. Herein, torsions were measured for cellooligosaccharides and lactose moieties complexed with proteins in the Protein Data Bank (PDB). These torsions were compared with ϕ/ψ maps based on quantum mechanics energies for solvated cellobiose and analogs lacking hydroxyl groups. Most PDB conformations corresponded to low map energies. Amorphous cellulose should be generally extended with individual linkages that would give 2- to 3-fold helices. The map for an analog lacking hydrogen bonding ability was more predictive for PDB linkages than the cellobiose map.

Evidence for repeated failure of the giant Yigong landslide on the edge of the Tibetan Plateau.

Field surveys and radiocarbon dating of detrital materials provide evidence that repeated landslides dammed the Yigong Tsangpo River ca. 3500 BC, 1300 BC, 1000 BC, 600 BC, and twice more recently. Together with historical slides in 1900 and 2000, these six older slides make for a total of eight known channel-damming landslide events at the same location over the past six millennia, indicating sub-millennia recurrence intervals over this time period. Together with the likely incomplete nature of the sedimentary record of past channel-damming episodes uncovered to date, our findings indicate late Holocene multi-century-scale recurrence intervals for large landslides at this location. Hence, the riverbed at and immediately upstream of this location may have been inundated by sediment, and therefore not incising, for much of the post-glacial period. Together with the location of this landslide complex at the head of the major knickzone defining the fluvial edge of the Tibetan Plateau, our findings support the hypothesis that repeated glacial and landslide damming in this region inhibited headward propagation of river incision into the Tibetan Plateau.

Analysis of the SARS-CoV-2 spike protein glycan shield reveals implications for immune recognition.

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the innate and adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the notable exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight of the S trimer (17% for the HEK293 glycoform) they shield approximately 40% of the protein surface.

Characterization of heparin and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) spike glycoprotein binding interactions.

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs may interact SARS-CoV-2 SGPs to facilitate host cell entry. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 SGP bind more tightly to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 µM, 0.12 µM, and 26.4 µM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. The current study serves a foundation to further investigate biological roles of GAGs in SARS-CoV-2 pathogenesis. Furthermore, our findings may provide additional basis for further heparin-based interventions for COVID-19 patients exhibiting thrombotic complications.

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition.

Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycoform) the level of surface shielding is disproportionately high at 42%.

The Longitudinal Parallel Process Analysis of Biomarkers of Oxidative Stress, Symptom Clusters, and Cognitive Function in Children With Leukemia.

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system-directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster-Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar punctures. GSH biomarkers, symptoms, and cognitive function of 132 children aged 3 to 18 years were evaluated at four time points during the first year of leukemia treatment. Participants, 7 years and older, completed self-report measures, and parents reported for younger children. Cognitive function measurements for all participants were completed by parents. A longitudinal parallel-process model was used to explore the influence of the initial measurement and the subsequent change over four time points of the GSH biomarkers on the CCSC-L and cognition. Results: GSH biomarkers increased over the four time points indicating decreasing oxidative stress. When GSH biomarkers were higher (less oxidative stress) at the initial measurement, the CCSC-L severity was lower, cognition was better, and cognition improved over the four measurements. Screening children for high levels of oxidative stress would be a foundation for future intervention studies to address symptom distress and cognitive impairments.