A5062141175- Adenosine and Purinergic Signaling
- Retinal Development and Disorders
- Neuroscience of respiration and sleep
- Retinal Diseases and Treatments
- Glaucoma and retinal disorders
- Connexins and lens biology
- Neuroscience and Neuropharmacology Research
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Retinopathy of Prematurity Studies
- Cellular transport and secretion
- Neonatal Health and Biochemistry
- Vagus Nerve Stimulation Research
- Inflammasome and immune disorders
- RNA Interference and Gene Delivery
- Neurological Complications and Syndromes
- Drug-Induced Ocular Toxicity
- Photoreceptor and optogenetics research
- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
- Nicotinic Acetylcholine Receptors Study
- Fibroblast Growth Factor Research
- Cholesterol and Lipid Metabolism
University of Pennsylvania
2015-2024
The Christie NHS Foundation Trust
2018-2024
Translational Therapeutics (United States)
2020-2024
California University of Pennsylvania
2021-2024
University of Wisconsin–Madison
2024
Penn Presbyterian Medical Center
2023
Altec (United States)
2021
Delsys (United States)
2021
Nationwide Children's Hospital
2018
The Christie Hospital
2018
Presenilin 1 (PS1) deletion or Alzheimer's disease (AD)-linked mutations disrupt lysosomal acidification and proteolysis, which inhibits autophagy. Here, we establish that this phenotype stems from impaired glycosylation instability of vATPase V0a1 subunit, causing deficient assembly function. We further demonstrate elevated pH in knockout (PS1KO) cells induces abnormal Ca(2+) efflux lysosomes mediated by TRPML1 elevates cytosolic Ca(2+). In WT cells, blocking activity knockdown either PS1...
Purines can modify ciliary epithelial secretion of aqueous humor into the eye. The source purinergic agonists acting in epithelium, as many tissues, is unknown. We found that fluorescent ATP marker quinacrine stained rabbit and bovine epithelia but not nerve fibers bodies. Cultured pigmented nonpigmented cells also intensely when incubated with quinacrine. Hypotonic stimulation cultured increased extracellular concentration by 3-fold; this measurement underestimates actual release displayed...
Mechanical deformation produces complex effects on neuronal systems, some of which can lead to dysfunction and death. While astrocytes are known respond mechanical forces, it is not clear whether neurons also directly. We examined mechanosensitive ATP release the physiological response this in isolated retinal ganglion cells. Purified cells released upon swelling. Release was blocked by carbenoxolone, probenecid or peptide (10)panx, implicating pannexin channels as conduits. stretch...
As adenosine 5′‐triphosphate (ATP) released from astrocytes can modulate many neural signaling systems, the triggers and pathways for this ATP release are important. Here, ability of mechanical strain to trigger through pannexin channels effects sustained on expression were examined in rat optic nerve head astrocytes. Astrocytes when subjected 5% equibiaxial or hypotonic swelling. Although expressed mRNA pannexins 1–3, connexin 43, VNUT, pharmacological analysis suggested a predominant role...
Inflammatory responses play a key role in many neural pathologies, with localized signaling from the non-immune cells making critical contributions. The NLRP3 inflammasome is an important component of innate immune and can link insult to chronic inflammation. requires two stages contribute: priming activation. stage involves upregulation components while activation results assembly complex. step be rate limiting connect inflammation, but our knowledge signals that regulate sterile...
Lysosomal enzymes function optimally in acidic environments, and elevation of lysosomal pH can impede their ability to degrade material delivered lysosomes through autophagy or phagocytosis. We hypothesize that abnormal is a key aspect diseases accumulation restoring will improve cell function. The propensity nanoparticles end up the lysosome makes them an ideal method delivering drugs lysosomes. This study asked whether could traffic lysosomes, lower enhance degradation by cultured human...
Postsurgical dental pain is mainly driven by inflammation, particularly through the generation of prostaglandins via cyclooxygenase system. Thus, it no surprise that numerous randomized placebo-controlled trials studying acute following surgical extraction impacted third molars have demonstrated remarkable efficacy nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen sodium, etodolac, diclofenac, and ketorolac in this prototypic condition inflammatory pain. Combining an...
Microglial cells regulate neural homeostasis by coordinating both immune responses and clearance of debris, the P2X7 receptor for extracellular ATP plays a central role in functions. The is primarily known microglial its signaling NLRP3 inflammasome activation. However, also affects intracellular debris through modifications lysosomal function, phagocytosis, autophagy. In absence an agonist, acts as scavenger to phagocytose material. Transient stimulation induces autophagy increases LC3-II...
Many Ca(2+) channel proteins have been detected in mammalian sperm, but only the four CATSPER channels clearly shown to be required for male fertility. entry through principal piece-localized has implicated activation of hyperactivated motility. In present study, we show that also triggers a tail-to-head propagation mouse sperm. When activated with 8-Br-cAMP, 8-Br-cGMP, or alkaline depolarization, CATSPER-dependent increase intracellular concentration starts piece, propagates midpiece, and...
Degradation of engulfed material is primarily mediated by lysosomal enzymes that function optimally within a narrow range acidic pH values. RPE cells are responsible for daily degradation photoreceptor outer segments and thus particularly susceptible to perturbations in pH. The authors hypothesized elevated levels could slow enzyme activity encourage accumulation partially digested material. Consequently, treatment lower perturbed may enhance degradative activity.A high-throughput screening...
Retinal ganglion cells are known to express ionotropic P2X(7) receptors for ATP. Stimulation of these in other can elevate Ca(2+) and sometimes lead cell death. This study asked whether receptor stimulation alters the levels viability retinal cells.P2X(7) agonists were applied from neonatal rats loaded with fura-2 examine their effect on intracellular levels. The was examined rat back-labeled aminostilbamidine.The agonist benzoylbenzoyl adenosine triphosphate (BzATP) led a large, sustained...
Contents: Introduction The 'sectarian headcount' churches and politics Religion as a boundary marker Religious practice community construction ideology Theology Conclusions Glossary of terms Appendix Notes Bibliography Index.
Lysosomal enzymes function optimally at low pH; as accumulation of waste material contributes to cell aging and disease, dysregulation lysosomal pH may represent an early step in several pathologies. Here, we demonstrate that stimulation the P2X7 receptor (P2X7R) for ATP alkalinizes lysosomes cultured human retinal pigmented epithelial (RPE) cells impairs function. P2X7R did not kill RPE but alkalinized by 0.3 U. Receptor also elevated cytoplasmic Ca2+; Ca2+ influx was necessary sufficient...
ATP is released through pannexin channels into the lumen of rat urinary bladder in response to distension or stimulation with bacterial endotoxins. Luminal plays a physiological role control micturition because intravesical perfusion apyrase ecto-ATPase inhibitor ARL67156 altered reflex activity anaesthetized rat. The release from apical and basolateral surfaces urothelium appears be mediated by separate mechanisms administration channel antagonist Brilliant Blue FCF increased capacity,...