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Full-Text Articles in Medicine and Health Sciences

Repeated Stressors In Adulthood Increase The Rate Of Biological Ageing, Michaela Hau, Mark F. Haussmann, Timothy J. Greives, Christa Matlack, David Costantini, Michael Quetting, James S. Adelman, Ana C. Miranda, Jesko Partecke Jan 2015

Repeated Stressors In Adulthood Increase The Rate Of Biological Ageing, Michaela Hau, Mark F. Haussmann, Timothy J. Greives, Christa Matlack, David Costantini, Michael Quetting, James S. Adelman, Ana C. Miranda, Jesko Partecke

James S. Adelman

Individuals of the same age can differ substantially in the degree to which they have accumulated tissue damage, akin to bodily wear and tear, from past experiences. This accumulated tissue damage reflects the individual’s biological age and may better predict physiological and behavioural performance than the individual‘s chronological age. However, at present it remains unclear how to reliably assess biological age in individual wild vertebrates. We exposed hand-raised adult Eurasian blackbirds (Turdus merula) to a combination of repeated immune and disturbance stressors for over one year to determine the effects of chronic stress on potential biomarkers of biological ageing including …


Protection Of Retinal Cells From Ischemia By A Novel Gap Junction Inhibitor, Satyabrata Das, Dingo Lin, Snehalata Jena, Aibin Shi, Srinivas Battina, Duy H. Hua, Rachel A. Allbaugh, Dolores J. Takemoto Sep 2008

Protection Of Retinal Cells From Ischemia By A Novel Gap Junction Inhibitor, Satyabrata Das, Dingo Lin, Snehalata Jena, Aibin Shi, Srinivas Battina, Duy H. Hua, Rachel A. Allbaugh, Dolores J. Takemoto

Rachel A. Allbaugh

Retinal cells which become ischemic will pass apoptotic signal to adjacent cells, resulting in the spread of damage. This occurs through open gap junctions. A class of novel drugs, based on primaquine (PQ), was tested for binding to connexin 43 using simulated docking studies. A novel drug has been synthesized and tested for inhibition of gap junction activity using R28 neuro-retinal cells in culture. Four drugs were initially compared to mefloquine, a known gap junction inhibitor. The drug with optimal inhibitory activity, PQ1, was tested for inhibition and was found to inhibit dye transfer by 70% at 10 μM. Retinal …


Bifunctional Abietadiene Synthase: Mutual Structural Dependence Of The Active Sites For Protonation-Initiated And Ionization-Initiated Cyclizations, Reuben J. Peters, Ora A. Carter, Yan Zhang, Brian W. Matthews, Rodney B. Croteau Mar 2003

Bifunctional Abietadiene Synthase: Mutual Structural Dependence Of The Active Sites For Protonation-Initiated And Ionization-Initiated Cyclizations, Reuben J. Peters, Ora A. Carter, Yan Zhang, Brian W. Matthews, Rodney B. Croteau

Reuben J. Peters

Abietadiene synthase from grand fir catalyzes two sequential, mechanistically distinct cyclizations, of geranylgeranyl diphosphate and of copalyl diphosphate, in the formation of a mixture of abietadiene isomers as the committed step of diterpenoid resin acid biosynthesis. Each reaction is independently conducted at a separate active site residing in what were considered to be structurally distinct domains typical of terpene cyclases. Despite the presence of an unusual 250-residue N-terminal insertional element, a tandem pair of charged residues distal to the insertion was shown to form a functional part of the C-terminal active site. Because abietadiene synthase resembles the ancestral plant terpene …


Mechanism Of Abietadiene Synthase Catalysis: Stereochemistry And Stabilization Of The Cryptic Pimarenyl Carbocation Intermediates, Reuben J. Peters, Matthew M. Ravn, Robert M. Coates, Rodney Croteau Jun 2002

Mechanism Of Abietadiene Synthase Catalysis: Stereochemistry And Stabilization Of The Cryptic Pimarenyl Carbocation Intermediates, Reuben J. Peters, Matthew M. Ravn, Robert M. Coates, Rodney Croteau

Reuben J. Peters

Abietadiene synthase (AS) catalyzes the complex cyclization-rearrangement of (E,E,E)-geranylgeranyl diphosphate (8, GGPP) to a mixture of abietadiene (1a), double bond isomers 2a-4a and pimaradienes 5a-7a as a key step in the biosynthesis of the abietane resin acid constituents (1b-4b) of conifer oleoresin. The reaction proceeds at two active sites by way of the intermediate, copalyl diphosphate (9). In the second site, a putative tricyclic pimaradiene or pimarenyl(+) carbocation intermediate of undefined C13 stereochemistry and annular double bond position is formed. Three 8-oxy-17-nor analogues of 9 (17 and 19a,b) and three isomeric 15,16-bisnorpimarenyl-N-methylamines (26a-c) were synthesized and evaluated as alternative substrates …


Abietadiene Synthase Catalysis:  Conserved Residues Involved In Protonation-Initiated Cyclization Of Geranylgeranyl Diphosphate To (+)-Copalyl Diphosphate, Reuben J. Peters, Rodney B. Croteau Feb 2002

Abietadiene Synthase Catalysis:  Conserved Residues Involved In Protonation-Initiated Cyclization Of Geranylgeranyl Diphosphate To (+)-Copalyl Diphosphate, Reuben J. Peters, Rodney B. Croteau

Reuben J. Peters

Abietadiene synthase catalyzes two sequential, mechanistically distinct cyclization reactions in the formation of a mixture of abietadiene double bond isomers as the committed step in resin acid biosynthesis. Each reaction is carried out at a separate active site residing in a structurally distinct domain, and the reactions are kinetically separable. The first cyclization reaction is initiated by protonation of the terminal double bond of the universal diterpene precursor, geranylgeranyl diphosphate. The pH dependence of the overall reaction is consistent with an acid-base catalytic mechanism, and a divalent metal ion plays a role in this reaction probably by binding the diphosphate …