- Nicotinic Acetylcholine Receptors Study
- Advanced Fluorescence Microscopy Techniques
- Extracellular vesicles in disease
- Receptor Mechanisms and Signaling
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Immune cells in cancer
- Neuroscience and Neuropharmacology Research
- Advanced biosensing and bioanalysis techniques
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Nanocluster Synthesis and Applications
- Advanced Biosensing Techniques and Applications
- Photonic and Optical Devices
- RNA Interference and Gene Delivery
- Nanoplatforms for cancer theranostics
- Quantum Dots Synthesis And Properties
- Phagocytosis and Immune Regulation
- Cellular Mechanics and Interactions
- Carbon and Quantum Dots Applications
- Monoclonal and Polyclonal Antibodies Research
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Heavy Metal Exposure and Toxicity
- Reproductive System and Pregnancy
University of Kentucky
2015-2024
Jacobs (United States)
2020
California Institute of Technology
2011-2012
Fluorescent carbon nanodots (CNDs) were synthesized in oxidized and reduced forms analyzed at the single-particle level. Images of single CNDs different excitation energies revealed significant heterogeneity lower energy trap sites between particles. We observed that a high percentage CND particles transitioned multiple fluorescence intensity levels indicative multichromophoric systems. Despite this behavior, individual exhibit single-step photobleaching transient blinking to background...
Chronic pain is a highly prevalent and poorly managed human health problem. We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors mechanical allodynia, prominent symptom of chronic pain. identified levels Chrna6, which encodes the α6 subunit nicotinic acetylcholine receptor (nAChR), as associated with allodynia. confirmed importance α6* (α6-containing) nAChRs by analyzing both gain- loss-of-function...
Abstract The “canonical” function of Pax7+ muscle stem cells (satellite cells) during hypertrophic growth adult fibers is myonuclear donation via fusion to support increased transcriptional output. In recent years, however, emerging evidence suggests that satellite play an important secretory role in promoting load-mediated growth. Utilizing genetically modified mouse models delayed cell and vivo extracellular vesicle (EV) tracking, we provide for communication hypertrophy. Myogenic...
Using
Chronic exposure to nicotine up-regulates high sensitivity nicotinic acetylcholine receptors (nAChRs) in the brain. This up-regulation partially underlies addiction and may also contribute protection against Parkinson’s disease. nAChRs containing α6 subunit (α6* nAChRs) are expressed neurons several brain regions, but comparatively little is known about effect of chronic on these nAChRs. We report here that α6* mouse regions (substantia nigra pars compacta, ventral tegmental area, medial...
Metal halide perovskite nanocrystals (NCs) are attractive materials for optoelectronics. However, further improvements in stability, reproducibility, and photoluminescence quantum yield (ΦPL) essential enabling future applications. Inadequate surface passivation is a major cause of instability, irreproducibility, less than unity ΦPL. Herein, we probe the influence multiple ligand binding groups on colloidal stability ΦPL CsPbBr3 (NCs). We find that post-synthetic treatment with dodecanethiol...
Unraveling the transport of drugs and nanocarriers in cerebrovascular networks is important for pharmacokinetic hemodynamic studies but challenging due to complexity sensing individual particles within circulatory system a live animal. Here, we demonstrate that DNA-stabilized silver nanocluster (DNA-Ag16NC) emits first near-infrared window upon two-photon excitation second NIR can be used multiphoton vivo fluorescence correlation spectroscopy measurement cerebral blood flow rates mice with...
We exploit the optical and spatial features of subwavelength nanostructures to examine individual receptors on plasma membrane living cells. Receptors were sequestered in portions projected into zero-mode waveguides. Using single-step photobleaching green fluorescent protein incorporated subunits, resulting isolation was used measure subunit stoichiometry α4β4 α4β2 nicotinic acetylcholine P2X2 ATP receptors. also show that nicotine cytisine have differential effects stoichiometry.
Glycosylphosphatidylinositol-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by the extracellular portion of nAChRs. These actions generally thought proceed when both and nAChRs on plasma membrane. Here, we demonstrate that lynx1 also exerts α4β2 within endoplasmic reticulum. Lynx1 affects assembly nascent α4 β2 subunits alters stoichiometry population reaches Additionally, these data suggest shifts...
We report the first observation that endoplasmic reticulum (ER) stress and unfolded protein response (UPR) can decrease when a central nervous system drug acts as an intracellular pharmacological chaperone for its classic receptor. Transient expression of α4β2 nicotinic receptors (nAChRs) in Neuro-2a cells induced nuclear translocation activating transcription factor 6 (ATF6), which is part UPR. Cells were exposed 48 h to full agonist nicotine, partial cytisine, or competitive antagonist...
The emissive properties of both doped and nondoped graphene quantum dots (GQDs) with sizes ranging from 3 to 11 nm were analyzed at the single particle level. Both GQDs are a composite particles exhibiting green, red, or NIR fluorescence on excitation 488, 561, 640 nm, respectively. Nitrogen-doped (N-GQDs) diameters 3.4 5.2 show larger proportion emission as compared particles. Doping also resulted in changes photostability intermittency seen GQD While milliseconds seconds time scale...
Abstract Background Skeletal muscle (SkM) is a large, secretory organ that produces and releases myokines can have autocrine, paracrine, endocrine effects. Whether extracellular vesicles (EVs) also play role in the SkM adaptive response ability to communicate with other tissues not well understood. The purpose of this study was investigate EV biogenesis factors, marker expression, localization across cell types skeletal muscle. We aimed whether concentrations are altered by disuse atrophy....
We employed a pH-sensitive GFP analog, superecliptic phluorin, to observe aspects of nicotinic acetylcholine receptor (nAChR) trafficking the plasma membrane (PM) in cultured mouse cortical neurons. The experiments exploit differences pH among endoplasmic reticulum (ER), vesicles, and extracellular solution. data confirm that few α4β4 nAChRs, but many α4β2 remain neutral intracellular compartments, mostly ER. observed fusion events between nAChR-containing vesicles PM; these could be...
Abstract Nicotine is a highly addictive compound present in tobacco, which causes the release of dopamine different regions brain. Recent studies have shown that astrocytes express nicotinic acetylcholine receptors (nAChRs) and mediate calcium signaling. In this study, we examine morphological functional adaptations due to nicotine exposure. Utilizing combination fluorescence atomic force microscopy, show nicotine‐treated exhibit time‐dependent remodeling number length both proximal fine...
Microglia act as the immune cells of central nervous system (CNS). They play an important role in maintaining brain homeostasis but also mediating neuroimmune responses to insult. The interactions between neurons and microglia represent a key process for regulation subsequent effects on CNS integrity. However, molecular mechanisms neuron-glia communication regulating function are not fully understood. One recently described means this intercellular is via nano-sized extracellular vesicles...
T cells play an integral role in the generation of effective immune response and are responsible for clearing foreign microbes that have bypassed innate system defenses possess cognate antigens. The can be directed toward a desired target through selective priming activation cells. Due to their ability activate cell response, dendritic endogenous vesicles from being developed cancer immunotherapy treatment. However, current platforms, such as exosomes synthetic nanoparticles, limited by...
Macrophages, one of the most important phagocytic cells immune system, are highly plastic and known to exhibit diverse roles under different pathological conditions. The ability repolarize macrophages from pro-inflammatory (M1) anti-inflammatory (M2) or vice versa offers a promising therapeutic approach for treating various diseases such as traumatic injury cancer. Herein, it is demonstrated that macrophage-engineered vesicles (MEVs) generated by disruption macrophage cellular membranes can...
Ca2+ is a major second messenger involved in cellular and subcellular signaling wide range of cells, including astrocytes, which use calcium ions to communicate with other cells the brain. Even though variety genetically encoded indicators have been developed study astrocyte signaling, understanding dynamics endoplasmic reticulum greatly limited by currently available tools. To address this, we an reticulum-targeted indicator, ER-GCaMP6f, anchored cytosolic side organelle measures that...
Abstract A new approach is presented for the application of single‐molecule imaging to membrane receptors through use vesicles derived from cells expressing fluorescently labeled receptors. During isolation vesicles, remain embedded in resultant thus allowing these serve as nanocontainers measurements. Cell‐derived maintain structural integrity transmembrane by keeping them their physiological membrane. It was demonstrated that isolated can be studied with solution‐based fluorescence...
Target identification and mechanistic studies of cytotoxic agents are challenging processes that both time-consuming costly. Here we describe an approach to mechanism action for potential anticancer compounds by utilizing the simple prokaryotic system, E. coli, demonstrate its utility with characterization a ruthenium polypyridyl complex [Ru(bpy)2dmbpy2+]. Expression photoconvertible fluorescent protein Dendra2 facilitated high throughput single-cell imaging. This allowed simultaneous...
The effect of gold and aluminum zero-mode waveguides (ZMWs) on the brightness immobilized single emitters was characterized by probing fluorophores that absorb in green red regions visible spectrum. Aluminum ZMWs enhance emission Atto565 upon excitation, but they do not Atto647N excitation. Gold increase both with showing enhancement is threefold higher than observed for Atto565. This work indicates 200 nm are better suited single-molecule fluorescence studies region spectrum, while appears more