Early evolution of the LIM homeobox gene family

Background: LIM homeobox (Lhx) transcription factors are unique to the animal lineage and have patterning roles during embryonic development in flies, nematodes and vertebrates, with a conserved role in specifying neuronal identity. Though genes of this family have been reported in a sponge and a cnidarian, the expression patterns and functions of the Lhx family during development in non-bilaterian phyla are not known

Exploring skeletal muscle tolerance and whole‐body metabolic effects of FDA‐approved drugs in a volumetric muscle loss model

Abstract Volumetric muscle loss (VML) is associated with persistent functional impairment due to a lack of de novo muscle regeneration. As mechanisms driving the lack of regeneration continue to be established, adjunctive pharmaceuticals to address the pathophysiology of the remaining muscle may offer partial remediation. Studies were designed to evaluate the tolerance and efficacy of two FDA‐approved pharmaceutical modalities to address the pathophysiology of the remaining muscle tissue after VML injury: (1) nintedanib (an anti‐fibrotic) and (2) combined formoterol and leucine (myogenic promoters). Tolerance was first established by testing low‐ and high‐dosage effects on uninjured skeletal muscle mass and myofiber cross‐sectional area in adult male C57BL/6J mice. Next, tolerated doses of the two pharmaceutical modalities were tested in VML‐injured adult male C57BL/6J mice after an 8‐week treatment period for their ability to modulate muscle strength and whole‐body metabolism. The most salient findings indicate that formoterol plus leucine mitigated the loss in muscle mass, myofiber number, whole‐body lipid oxidation, and muscle strength, and resulted in a higher whole‐body metabolic rate (p ≤ 0.016); nintedanib did not exacerbate or correct aspects of the muscle pathophysiology after VML. This supports ongoing optimization efforts, including scale‐up evaluations of formoterol treatment in large animal models of VML

Hydrogel Nanosensors for Colorimetric Detection and Dosimetry in Proton Beam Radiotherapy

Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristic of protons, which results in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Currently available dosimeters are intrinsic, complex, and expensive and are not routinely used to determine the dose delivered to the tumor. Here, we report a hydrogel-based plasmonic nanosensor for detecting clinical doses used in conventional and hyperfractionated proton beam radiotherapy. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during proton treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime, and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy