An Activity-Based Nanosensor for Traumatic Brain Injury.

Currently, traumatic brain injury (TBI) is detected by medical imaging; however, medical imaging requires expensive capital equipment, is time- and resource-intensive, and is poor at predicting patient prognosis. To date, direct measurement of elevated protease activity has yet to be utilized to detect TBI. In this work, we engineered an activity-based nanosensor for TBI (TBI-ABN) that responds to increased protease activity initiated after brain injury. We establish that a calcium-sensitive protease, calpain-1, is active in the injured brain hours within injury. We then optimize the molecular weight of a nanoscale polymeric carrier to infiltrate into the injured brain tissue with minimal renal filtration. A calpain-1 substrate that generates a fluorescent signal upon cleavage was attached to this nanoscale polymeric carrier to generate an engineered TBI-ABN. When applied intravenously to a mouse model of TBI, our engineered sensor is observed to locally activate in the injured brain tissue. This TBI-ABN is the first demonstration of a sensor that responds to protease activity to detect TBI

Nanomedicine for Acute Brain Injuries: Insight from Decades of Cancer Nanomedicine

Acute brain injuries such as traumatic brain injury and stroke affect 85 million people a year worldwide, and many survivors suffer from long-term physical, cognitive, or psychosocial impairments. There are few FDA-approved therapies that are effective at preventing, halting, or ameliorating the state of disease in the brain after acute brain injury. To address this unmet need, one potential strategy is to leverage the unique physical and biological properties of nanomaterials. Decades of cancer nanomedicine research can serve as a blueprint for innovation in brain injury nanomedicines, both to emulate the successes and also to avoid potential pitfalls. In this review, we discuss how shared disease physiology between cancer and acute brain injuries can inform the design of novel nanomedicines for acute brain injuries. These disease hallmarks include dysregulated vasculature, an altered microenvironment, and changes in the immune system. We discuss several nanomaterial strategies that can be engineered to exploit these disease hallmarks, for example, passive accumulation, active targeting of disease-associated signals, bioresponsive designs that are "smart", and immune interactions

Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury

Peptides are used to control the pharmacokinetic profiles of nanoparticles due to their ability to influence tissue accumulation and cellular interactions. However, beyond the study of specific peptides, there is a lack of understanding of how peptide physicochemical properties affect nanoparticle pharmacokinetics, particularly in the context of traumatic brain injury (TBI). We engineered nanoparticle surfaces with peptides that possess a range of physicochemical properties and evaluated their distribution after two routes of administration: direct injection into a healthy mouse brain and systemic delivery in a mouse model of TBI. In both administration routes, we found that peptide-modified nanoparticle pharmacokinetics were influenced by the charge characteristics of the peptide. When peptide-modified nanoparticles are delivered directly into the brain, nanoparticles modified with positively charged peptides displayed restricted distribution from the injection site compared to nanoparticles modified with neutral, zwitterionic, or negatively charged peptides. After intravenous administration in a TBI mouse model, positively charged peptide-modified nanoparticles accumulated more in off-target organs, including the heart, lung, and kidneys, than zwitterionic, neutral, or negatively charged peptide-modified nanoparticles. The increase in off-target organ accumulation of positively charged peptide-modified nanoparticles was concomitant with a relative decrease in accumulation in the injured brain compared to zwitterionic, neutral, or negatively charged peptide-modified nanoparticles. Understanding how nanoparticle pharmacokinetics are influenced by the physicochemical properties of peptides presented on the nanoparticle surface is relevant to the development of nanoparticle-based TBI therapeutics and broadly applicable to nanotherapeutic design, including synthetic nanoparticles and viruses

U.S. cereal rye winter cover crop growth database

Abstract Winter cover crop performance metrics (i.e., vegetative biomass quantity and quality) affect ecosystem services provisions, but they vary widely due to differences in agronomic practices, soil properties, and climate. Cereal rye (Secale cereale) is the most common winter cover crop in the United States due to its winter hardiness, low seed cost, and high biomass production. We compiled data on cereal rye winter cover crop performance metrics, agronomic practices, and soil properties across the eastern half of the United States. The dataset includes a total of 5,695 cereal rye biomass observations across 208 site-years between 2001–2022 and encompasses a wide range of agronomic, soils, and climate conditions. Cereal rye biomass values had a mean of 3,428 kg ha−1, a median of 2,458 kg ha−1, and a standard deviation of 3,163 kg ha−1. The data can be used for empirical analyses, to calibrate, validate, and evaluate process-based models, and to develop decision support tools for management and policy decisions

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu