POU6f1 Mediates Neuropeptide-Dependent Plasticity in the Adult Brain.

The mouse olfactory bulb (OB) features continued, activity-dependent integration of adult-born neurons, providing a robust model with which to examine mechanisms of plasticity in the adult brain. We previously reported that local OB interneurons secrete the neuropeptide corticotropin-releasing hormone (CRH) in an activity-dependent manner onto adult-born granule neurons and that local CRH signaling promotes expression of synaptic machinery in the bulb. This effect is mediated via activation of the CRH receptor 1 (CRHR1), which is developmentally regulated during adult-born neuron maturation. CRHR1 is a GS-protein-coupled receptor that activates CREB-dependent transcription in the presence of CRH. Therefore, we hypothesized that locally secreted CRH activates CRHR1 to initiate circuit plasticity programs. To identify such programs, we profiled gene expression changes associated with CRHR1 activity in adult-born neurons of the OB. Here, we show that CRHR1 activity influences expression of the brain-specific Homeobox-containing transcription factor POU Class 6 Homeobox 1 (POU6f1). To elucidate the contributions of POU6f1 toward activity-dependent circuit remodeling, we targeted CRHR1+ neurons in male and female mice for cell-type-specific manipulation of POU6f1 expression. Whereas loss of POU6f1 in CRHR1+ neurons resulted in reduced dendritic complexity and decreased synaptic connectivity, overexpression of POU6f1 in CRHR1+ neurons promoted dendritic outgrowth and branching and influenced synaptic function. Together, these findings suggest that the transcriptional program directed by POU6f1 downstream of local CRH signaling in adult-born neurons influences circuit dynamics in response to activity-dependent peptide signaling in the adult brain.SIGNIFICANCE STATEMENT Elucidating mechanisms of plasticity in the adult brain is helpful for devising strategies to understand and treat neurodegeneration. Circuit plasticity in the adult mouse olfactory bulb is exemplified by both continued cell integration and synaptogenesis. We previously reported that these processes are influenced by local neuropeptide signaling in an activity-dependent manner. Here, we show that local corticotropin-releasing hormone (CRH) signaling induces dynamic gene expression changes in CRH receptor expressing adult-born neurons, including altered expression of the transcription factor POU6f1 We further show that POU6f1 is necessary for proper dendrite specification and patterning, as well as synapse development and function in adult-born neurons. Together, these findings reveal a novel mechanism by which peptide signaling modulates adult brain circuit plasticity.

Advances in non-invasive biosensing measures to monitor wound healing progression.

Impaired wound healing is a significant financial and medical burden. The synthesis and deposition of extracellular matrix (ECM) in a new wound is a dynamic process that is constantly changing and adapting to the biochemical and biomechanical signaling from the extracellular microenvironments of the wound. This drives either a regenerative or fibrotic and scar-forming healing outcome. Disruptions in ECM deposition, structure, and composition lead to impaired healing in diseased states, such as in diabetes. Valid measures of the principal determinants of successful ECM deposition and wound healing include lack of bacterial contamination, good tissue perfusion, and reduced mechanical injury and strain. These measures are used by wound-care providers to intervene upon the healing wound to steer healing toward a more functional phenotype with improved structural integrity and healing outcomes and to prevent adverse wound developments. In this review, we discuss bioengineering advances in 1) non-invasive detection of biologic and physiologic factors of the healing wound, 2) visualizing and modeling the ECM, and 3) computational tools that efficiently evaluate the complex data acquired from the wounds based on basic science, preclinical, translational and clinical studies, that would allow us to prognosticate healing outcomes and intervene effectively. We focus on bioelectronics and biologic interfaces of the sensors and actuators for real time biosensing and actuation of the tissues. We also discuss high-resolution, advanced imaging techniques, which go beyond traditional confocal and fluorescence microscopy to visualize microscopic details of the composition of the wound matrix, linearity of collagen, and live tracking of components within the wound microenvironment. Computational modeling of the wound matrix, including partial differential equation datasets as well as machine learning models that can serve as powerful tools for physicians to guide their decision-making process are discussed.

Strategies to Minimize Surgical Scarring: Translation of Lessons Learned from Bedside to Bench and Back.

Significance: An understanding of the physiology of wound healing and scarring is necessary to minimize surgical scar formation. By reducing tension across the healing wound, eliminating excess inflammation and infection, and encouraging perfusion to healing areas, surgeons can support healing and minimize scarring. Recent Advances: Preoperatively, newer techniques focused on incision placement to minimize tension, skin sterilization to minimize infection and inflammation, and control of comorbid factors to promote a healing process with minimal scarring are constantly evolving. Intraoperatively, measures like layered closure, undermining, and tissue expansion can be taken to relieve tension across the healing wound. Appropriate suture technique and selection should be considered, and finally, there are new surgical technologies available to reduce tension across the closure. Postoperatively, the healing process can be supported as proliferation and remodeling take place within the wound. A balance of moisture control, tension reduction, and infection prevention can be achieved with dressings, ointments, and silicone. Vitamins and corticosteroids can also affect the scarring process by modulating the cellular factors involved in healing. Critical Issues: Healing with no or minimal scarring is the ultimate goal of wound healing research. Understanding how mechanical tension, inflammation and infection, and perfusion and hypoxia impact profibrotic pathways allows for the development of therapies that can modulate cytokine response and the wound extracellular microenvironment to reduce fibrosis and scarring. Future Directions: New tension-off loading topical treatments, laser, and dermabrasion devices are under development, and small molecule therapeutics have demonstrated scarless wound healing in animal models, providing a promising new direction for future research aimed to minimize surgical scarring.

Online Resources in Plastic Surgery Education: A Toolbox for Modern Trainees and Plastic Surgeons.

Plastic surgery is a rapidly evolving field that requires novel approaches in providing continuous and dynamic educational resources to address the increasing time and skill demands from residents. Online resources in their various forms, such as books, journals, simulators, and applications, are increasingly used by residents, notably over traditional print and in-person counterparts. In this digital era, it is imperative to understand the scope and utility of online resources that have the potential to revolutionize plastic surgery education. In this review article, we first discuss the current model of plastic surgery education and the challenges of meeting its goals and then suggest reasons by which online resources close this gap. We also offer an exposition on the benefits of distinct types of resources and current trends regarding their use. Our goal is to create a framework within which learners and educators are able to organize online resources in plastic surgery.