Caspase-3 Cleaves Extracellular Vesicle Proteins During Auditory Brainstem Development.

Sound localization requires extremely precise development of auditory brainstem circuits, the molecular mechanisms of which are largely unknown. We previously demonstrated a novel requirement for non-apoptotic activity of the protease caspase-3 in chick auditory brainstem development. Here, we used mass spectrometry to identify proteolytic substrates of caspase-3 during chick auditory brainstem development. These auditory brainstem caspase-3 substrates were enriched for proteins previously shown to be cleaved by caspase-3, especially in non-apoptotic contexts. Functional annotation analysis revealed that our caspase-3 substrates were also enriched for proteins associated with several protein categories, including proteins found in extracellular vesicles (EVs), membrane-bound nanoparticles that function in intercellular communication. The proteome of EVs isolated from the auditory brainstem was highly enriched for our caspase-3 substrates. Additionally, we identified two caspase-3 substrates with known functions in axon guidance, namely Neural Cell Adhesion Molecule (NCAM) and Neuronal-glial Cell Adhesion Molecule (Ng-CAM), that were found in auditory brainstem EVs and expressed in the auditory pathway alongside cleaved caspase-3. Taken together, these data suggest a novel developmental mechanism whereby caspase-3 influences auditory brainstem circuit formation through the proteolytic cleavage of extracellular vesicle (EV) proteins.

Marjolin's ulcer: modern analysis of an ancient problem.

BACKGROUND: Marjolin's ulcer is a rare but highly aggressive squamous cell cancer that is most often associated with chronic burn wounds. Although many individual case reports exist, no thorough evaluation of Marjolin's ulcer patients has been conducted to date. METHODS: The authors present their experience with 10 patients encountered over a period of 15 years and analyze 25 previous publications, for a total of 443 patients diagnosed with Marjolin's ulcer. RESULTS: Although burn scar represents 76.5 percent of patients in the authors' review, venous stasis ulcers, traumatic wounds, osteomyelitis, and pressure sores are also represented as wound types that can undergo malignant degeneration. CONCLUSIONS: The authors' review suggests that there is much variability in the anatomical location of Marjolin's ulcers, with the majority occurring in wounds of the upper and lower extremities. Marjolin's ulcer appears to be preventable if early wound coverage is undertaken. Countries with limited access to medical treatment report a high number of Marjolin's ulcers compared with more developed regions.

Massive ventral hernias: role of tissue expansion in abdominal wall restoration following abdominal compartment syndrome.

Massive ventral hernias may result from a variety of clinical situations. One such clinical situation, a common problem in trauma patients, is abdominal compartment syndrome. Abdominal compartment syndrome frequently results in a massive abdominal defect when primary closure after surgical decompression is not possible. We offer a technique for repairing these massive ventral hernias by first expanding the lateral abdominal wall muscles, fasciae, and skin with tissue expanders and then closing the defect with elements of the "components separation" method. Additionally we present other clinical situations resulting in a massive ventral hernia that were repaired using this technique.