Quantification of Proliferating and Mitotically Active Retinal Cells in Mice by Flow Cytometry.

Adult mammals lack the ability to regenerate retinal neurons after injury. However, in previous studies from this lab, topical application of the selective alpha7 nicotinic acetylcholine receptor (nAChR) agonist, PNU-282987, has been associated with an increase in the number of retinal neurons in adult murine models both in the presence and absence of injury to the retina. Additionally, studies assaying mitotic markers have shown a substantial increase in the amount of mitotically active and proliferating cells with the topical application of the alpha7 nAChR agonist.

Acoustic arrival predictions using oceanographic measurements and models in the Beaufort Sea.

Acoustic propagation in the Beaufort Sea is particularly sensitive to upper-ocean sound-speed structure due to the presence of a subsurface duct known as the Beaufort duct. Comparisons of acoustic predictions based on existing Arctic models with predictions based on in situ data collected by Seaglider vehicles in the summer of 2017 show differences in the strength, depth, and number of ducts, highlighting the importance of in situ data. These differences have a significant effect on the later, more intense portion of the acoustic time front referred to as reverse geometric dispersion, where lower-order modes arrive prior to the final cutoff.

Age-related changes in antigen-specific natural antibodies are influenced by sex.

Introduction: Natural antibody (NAb) derived from CD5+ B-1 cells maintains tissue homeostasis, controls inflammation, aids in establishing long-term protective responses against pathogens, and provides immediate protection from infection. CD5+ B-1 cell NAbs recognize evolutionarily fixed epitopes, such as phosphatidylcholine (PtC), found on bacteria and senescent red blood cells. Anti-PtC antibodies are essential in protection against bacterial sepsis.

Functional Changes in the Adult Mouse Retina using an Alpha7 Nicotinic Acetylcholine Receptor Agonist after Blast Exposure.

Currently, there is a lack of treatments for retinal neurotrauma. To address this issue, this study uses an alpha7 nAChR agonist, PNU-282987, to determine it effects on functional activity in the retina shortly after a traumatic blast exposure. The objectives of this research include: (1) examination of the cellular and functional damage associated with ocular blast exposure, and (2) evaluation of structural and functional changes that occur post PNU-282987 treatment.

Transcriptome Changes in Retinal Pigment Epithelium Post-PNU-282987 Treatment Associated with Adult Retinal Neurogenesis in Mice.

PNU-282987, a selective alpha7 nicotinic acetylcholine receptor agonist, has previously been shown to have both neurogenic and broad regenerative effects in the adult murine retina. The objective of this study was to assay the molecular mechanism by which PNU-282987 promotes the production of Muller-derived progenitor cells through signaling via the resident retinal pigment epithelium. These Muller-derived progenitor cells generate a myriad of differentiated neurons throughout the retina that have previously been characterized by morphology.

Sex Influences Age-Related Changes in Natural Antibodies and CD5 B-1 Cells.

Natural Abs are primarily produced by B-1 cells and are essential for protection against The incidence and mortality rate for pneumococcal infection increases dramatically after age 65, disproportionately affecting males in both human and murine systems. To date, there is a significant gap in our understanding of the relationship among sex, aging, natural IgM efficacy, and the natural IgM repertoire. Our investigation demonstrates that the protective capacity of serum IgM against pneumococcal infection is maintained in IgM obtained from aged female mice but absent in IgM from aged male mice.

Modulation of microbiome diversity and cytokine expression is influenced in a sex-dependent manner during aging.

The microbiome and immune system have a unique interplay, which influences homeostasis within the organism. Both the microbiome and immune system play important roles in health and diseases of the aged including development of cancer, autoimmune disorders, and susceptibility to infection. Various groups have demonstrated divergent changes in the gut microbiota during aging, yet the compounding factor of biological sex within the context of aging remains incompletely understood, and little is known about the effect of housing location in the composition of gut microbiota in the context of both sex and age.

Stimulation of α7 nAChR leads to regeneration of damaged neurons in adult mammalian retinal disease models.

The adult mammal lacks the ability to regenerate neurons lost to retinal damage or disease in a meaningful capacity. However, previous studies from this laboratory have demonstrated that PNU-282987, an α7 nicotinic acetylcholine receptor agonist, elicits a robust neurogenic response in the adult murine retina. With eye drop application of PNU-282987, Müller glia cells re-enter the cell cycle and produce progenitor-like cells that can differentiate into various types of retinal neurons.

Involvement of Genes in Dedifferentiation of Adult Mammalian Müller Glia.

Previous studies from this lab have determined that dedifferentiation of Müller glia occurs after eye drop application of an α7 nicotinic acetylcholine receptor (nAChR) agonist, PNU-282987, to the adult rodent eye. PNU-282987 acts on α7 nAChRs on retinal pigment epithelial cells to stimulate production of Müller-derived progenitor cells (MDPCs) and ultimately lead to neurogenesis. This current study was designed to test the hypothesis that the activation of genes involved in the signaling pathway in Müller glia leads to the genesis of MDPCs.

Stimulation of Retinal Pigment Epithelium With an α7 nAChR Agonist Leads to Müller Glia Dependent Neurogenesis in the Adult Mammalian Retina.

Purpose: The adult mammalian retina is typically incapable of regeneration when damaged by disease or trauma. Restoration of function would require generation of new adult neurons, something that until recently, mammals were thought to be incapable of doing. However, previous studies from this laboratory have shown that the α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, PNU-282987, induces cell cycle reentry of Müller glia and generation of mature retinal neurons in adult rats, in the absence of detectible injury.

Eye Drops for Delivery of Bioactive Compounds and BrdU to Stimulate Proliferation and Label Mitotically Active Cells in the Adult Rodent Retina.

Eye drop treatments are typically used to apply drugs to the anterior structures of the eye. Recently, however, studies have demonstrated that eye drops can reach the retina in the back of the eye if pharmacological agents are carried in appropriate vehicles. Here, we introduce an eye drop procedure to deliver a drug (PNU-282987), in combination with BrdU, to stimulate cell cycle re-entry and label dividing cells in the retinas of adult rodents.

Evidence of BrdU-positive retinal neurons after application of an Alpha7 nicotinic acetylcholine receptor agonist.

Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. Using antibodies against BrdU, retinal ganglion cells, progenitor cells and Müller glia, the results of this study demonstrate that multiple types of retinal cells and neurons are generated after eye drop application of PNU-282987 in adult Long Evans rats in a dose-dependent manner.

Progressive loss of RacGAP1/ogre activity has sequential effects on cytokinesis and zebrafish development.

RacGAP1 is one of the two components of the centralspindlin complex essential for orchestrating cytokinesis in all animal cells. We report here that the early arrest mutant ogre is a maternal and zygotic loss of function mutation in the zebrafish homolog of racgap1. Like the other model organisms in which racgap1 is mutated, cells in the mutant stop dividing.