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The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett Oct 2020

The Acute Effects Of The Atypical Dissociative Hallucinogen Salvinorin A On Functional Connectivity In The Human Brain, Manoj K. Doss, Darrick G. May, Matthew W. Johnson, John M. Clifton, Sidnee L. Hedrick, Thomas E. Prisinzano, Roland R. Griffiths, Frederick S. Barrett

Pharmaceutical Sciences Faculty Publications

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the …


A Thorough Analysis And Categorization Of Bacterial Interrupted Adenylation Domains, Including Previously Unidentified Families, Taylor A. Lundy, Shogo Mori, Sylvie Garneau-Tsodikova Oct 2020

A Thorough Analysis And Categorization Of Bacterial Interrupted Adenylation Domains, Including Previously Unidentified Families, Taylor A. Lundy, Shogo Mori, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Interrupted adenylation (A) domains are key to the immense structural diversity seen in the nonribosomal peptide (NRP) class of natural products (NPs). Interrupted A domains are A domains that contain within them the catalytic portion of another domain, most commonly a methylation (M) domain. It has been well documented that methylation events occur with extreme specificity on either the backbone (N-) or side chain (O- or S-) of the amino acid (or amino acid-like) building blocks of NRPs. Here, through taxonomic and phylogenetic analyses as well as multiple sequence alignments, we evaluated the similarities and …


Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu Sep 2020

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …


Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto Sep 2020

Everything Is Science: A Free City-Wide Science Festival, Jarrod W. Creameans, Michelle G. Pitts, Olivia White, Kellen M. Greenwell, Kristie Colón, Sylvie Garneau-Tsodikova, Vincent J. Venditto

Pharmaceutical Sciences Faculty Publications

A week-long, city-wide science festival called Everything is Science (EiS) was developed to educate the community in an informal manner. The festival serves as a platform for presenters from diverse professions to give engaging talks (without PowerPoint slides) to the public, free of charge, in restaurants and bars around town. Over 350 people attended the events over 5 days with 33 presenters. Surveys completed by attendees and session coordinators indicate strong support for this festival. Altogether, the EiS festival serves as a no-cost method to engage with the community and improve science literacy with potential for adoption in other cities.


Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder Sep 2020

Methods For Using Nhanes For Exposure Estimates, Heather R. Campbell, Robert A. Lodder

Pharmaceutical Sciences Faculty Publications

The National Health and Nutrition Examination Survey (NHANES) is a scheme of studies with the objective of measuring the health and nutritional status of adults and children in the United States. The survey is unique in that it has a clinical component (NCT00005154), and combines interviews and physical examinations into its data sets. NHANES is an important program of the National Center for Health Statistics (NCHS). NCHS is a unit of the Centers for Disease Control and Prevention (CDC) and has the responsibility for producing vital and health statistics for the United States. Data from the NHANES studies …


Application Of Enzymes In Regioselective And Stereoselective Organic Reactions, Ruipu Mu, Zhaoshuai Wang, Max C. Wamsley, Colbee N. Duke, Payton H. Lii, Sarah E. Epley, London C. Todd, Patty J. Roberts Jul 2020

Application Of Enzymes In Regioselective And Stereoselective Organic Reactions, Ruipu Mu, Zhaoshuai Wang, Max C. Wamsley, Colbee N. Duke, Payton H. Lii, Sarah E. Epley, London C. Todd, Patty J. Roberts

Pharmaceutical Sciences Faculty Publications

Nowadays, biocatalysts have received much more attention in chemistry regarding their potential to enable high efficiency, high yield, and eco-friendly processes for a myriad of applications. Nature’s vast repository of catalysts has inspired synthetic chemists. Furthermore, the revolutionary technologies in bioengineering have provided the fast discovery and evolution of enzymes that empower chemical synthesis. This article attempts to deliver a comprehensive overview of the last two decades of investigation into enzymatic reactions and highlights the effective performance progress of bio-enzymes exploited in organic synthesis. Based on the types of enzymatic reactions and enzyme commission (E.C.) numbers, the enzymes discussed in …


Evaluation Of Biased And Balanced Salvinorin A Analogs In Preclinical Models Of Pain, Kelly F. Paton, Andrew Biggerstaff, Sophia Kaska, Rachel S. Crowley, Anne C. La Flamme, Thomas E. Prisinzano, Bronwyn M. Kivell Jul 2020

Evaluation Of Biased And Balanced Salvinorin A Analogs In Preclinical Models Of Pain, Kelly F. Paton, Andrew Biggerstaff, Sophia Kaska, Rachel S. Crowley, Anne C. La Flamme, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists. The present study investigated KOPr signaling bias and the acute antinociceptive effects and side effects of two novel analogs of SalA, 16-Bromo SalA and 16-Ethynyl SalA. 16-Bromo …


Nanoparticle Brain Delivery: A Guide To Verification Methods, Robert A. Yokel Feb 2020

Nanoparticle Brain Delivery: A Guide To Verification Methods, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Many reports conclude nanoparticle (NP) brain entry based on bulk brain analysis. Bulk brain includes blood, cerebrospinal fluid and blood vessels within the brain contributing to the blood-brain and blood-cerebrospinal fluid barriers. Considering the brain as neurons, glia and their extracellular space (brain parenchyma), most studies did not show brain parenchymal NP entry. Blood-brain and blood-cerebrospinal fluid barriers anatomy and function are reviewed. Methods demonstrating brain parenchymal NP entry are presented. Results demonstrating bulk brain versus brain parenchymal entry are classified. Studies are reviewed, critiqued and classified to illustrate results demonstrating bulk brain versus parenchymal entry. Brain, blood and peripheral …