Organisms Commons^™

Primary Cilium-Dependent Signaling Mechanisms, Rajasekharreddy Pala, Nedaa Alomari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like organelles and play crucial roles in vertebrate development, organogenesis, health, and many genetic disorders. A primary cilium is a mechano-sensory organelle that responds to mechanical stimuli in the micro-environment. A cilium is also a chemosensor that senses chemical signals surrounding a cell. The overall function of a cilium is therefore to act as a communication hub to transfer extracellular signals into intracellular responses. Although intracellular calcium has been one of the most studied signaling messengers that transmit extracellular signals into the cells, calcium signaling by various ion channels remains a topic of interest in the field. …

Alcohol Consumption Impairs The Ependymal Cilia Motility In The Brain Ventricles, Alzahra J. Al Omran, Hannah C. Saternos, Yusuf S. Althobaiti, Alexander Wisner, Youssef Sari, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Ependymal cilia protrude into the central canal of the brain ventricles and spinal cord to circulate the cerebral spinal fluid (CSF). Ependymal cilia dysfunction can hinder the movement of CSF leading to an abnormal accumulation of CSF within the brain known as hydrocephalus. Although the etiology of hydrocephalus was studied before, the effects of ethanol ingestion on ependymal cilia function have not been investigated in vivo. Here, we report three distinct types of ependymal cilia, type-I, type-II and type-III classified based upon their beating frequency, their beating angle, and their distinct localization within the mouse brain-lateral ventricle. Our studies …

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Pharmacy Faculty Articles and Research

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …

Pharmacodynamic Activity Of Fosfomycin Simulating Urinary Concentrations Achieved After A Single 3 Gram Oral Dose Versus Escherichia Coli Using An In Vitro Model, George G. Zhanel, Kate Parkinson, Sean Higgins, Andrew Denisuik, Heather Adam, Johann Pitout, Ayman Noreddin, James A. Karlowsky

Pharmacy Faculty Articles and Research

We assessed the activity of fosfomycin simulating urinary concentrations achieved after a single 3 gram oral dose against Escherichia coli using an in vitro pharmacodynamic model. Eleven urinary isolates of E. coli were studied. Isolates were ESBL-producing or carbapenemase-producing. The in vitro pharmacodynamic model was inoculated with an inoculum of (~1 × 10⁶ cfu/mL). Fosfomycin was administered to simulate maximum free (ƒ) urine (U) concentrations and a t_1/2 obtained after a standard single 3 gram oral dose in healthy volunteers (ƒU_max, 4000 mg/L; t_1/2, 6 h). Sampling was performed over 48 h to assess …

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …