subject:(Drug receptors)

University of Utah

1. Roalstad, Shelly M. Receptor dynamics in virtual screening: A dihydrofolate reductase case study.

Degree: MS;, Pharmaceutics & Pharmaceutical Chemistry;, 2007, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1634/rec/956

► The implications of receptor dynamics virtual screening were explored as part of proof of concept study for an interactive docking, molecular dynamics and scoring strategy.… (more)

▼ The implications of receptor dynamics virtual screening were explored as part of proof of concept study for an interactive docking, molecular dynamics and scoring strategy. The original study was to demonstrate whether or not the iterative process proposed would relax receptor structures that began as apo (without drug) or homology models toward known holo (with drug) coordinates. Due to species differences in the original receptor test systems, the study was refined to a set of well characterized dihydrofolate reductase (DHFR) receptors. Since both apo and holo structures were not available for each DHFR receptor selected, the goal of relaxing an apo structure toward a holo structure was modified. Various complexes of enzymes, ligand and cofactor were constructed to represent intermediates in the catalytic cycle know to adopt distinct conformations, and the new goal was to demonstrate movement toward one of these conformations during molecular dynamics simulations. Additionally, drug resistant E. coli DHFR and human DHFR structures were selected to probe the possible flexibility differences giving rise to enzymatic activity. Traditional molecular dynamics simulations demonstrated correct conformational change for one enzyme cofactor complex after 70 nanoseconds of simulation. Overall, relatively few complexes experienced any conformational change, indicating the need for longer trajectories or more advanced simulation techniques. Flexible regions of the enzyme described in literature were correctly depicted by trajectory analysis. Flexibility differences between bacterial and vertebrate DHFR showed bacterial DHFR to have more localized movements of three flexible loops and vertebrate DHFR more disperse flexibility. Evaluating the free energy of binding by Molecular Mechanics – Poisson Boltzmann Surface Area (MM-PBSA) methods was shown to be more insightful when employed before and after conformational change rather than over an entire trajectory. Ligand binding values generally independent of enzyme activity demonstrated the necessity of considering binding in the context of the catalytic cycle. Traditional molecular dynamics demonstrated the capability of moving a receptor toward a known conformation, through the resolution of conformational change was depended on the amount of trajectory available. Advanced molecular dynamics methods possible capable of expediting conformational change are proposed for future studies.

Subjects/Keywords: Drug Receptors; Drugs:

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roalstad, S. M. (2007). Receptor dynamics in virtual screening: A dihydrofolate reductase case study. (Masters Thesis). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1634/rec/956

Chicago Manual of Style (16^th Edition):

Roalstad, Shelly M. “Receptor dynamics in virtual screening: A dihydrofolate reductase case study.” 2007. Masters Thesis, University of Utah. Accessed March 07, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1634/rec/956.

MLA Handbook (7^th Edition):

Roalstad, Shelly M. “Receptor dynamics in virtual screening: A dihydrofolate reductase case study.” 2007. Web. 07 Mar 2021.

Vancouver:

Roalstad SM. Receptor dynamics in virtual screening: A dihydrofolate reductase case study. [Internet] [Masters thesis]. University of Utah; 2007. [cited 2021 Mar 07]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1634/rec/956.

Council of Science Editors:

Roalstad SM. Receptor dynamics in virtual screening: A dihydrofolate reductase case study. [Masters Thesis]. University of Utah; 2007. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1634/rec/956

2. Visic, Petra. The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains.

Degree: PhD, 2020, University of Sussex

URL: http://sro.sussex.ac.uk/id/eprint/90959/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804978

► The Sigma1 receptor (σ1R) is an endoplasmic reticulum (ER) chaperone targeted to mitochondrion associated ER membranes (MAMs). The upregulation of σ1R is associated with various… (more)

▼ The Sigma1 receptor (σ1R) is an endoplasmic reticulum (ER) chaperone targeted to mitochondrion associated ER membranes (MAMs). The upregulation of σ1R is associated with various cancers, whereas the decreased expression and mutant forms of σ1R are associated with neurodegenerative disorders. The underlying cellular mechanism by which σ1R exerts such a versatile impact remains elusive. At MAMs, σ1R is reported to regulate inter-organelle Ca2+ levels. Following translocation to ER-plasma membrane junctions, σ1R is reported to interact with various ion channels, including the key regulators of store-operated Ca2+ entry (SOCE). I have investigated the role of σ1R in the regulation of SOCE within a population of cells and within the SOCE microdomains of single cells. In a population of cells, overexpression of σ1R profoundly inhibited both Ca2+ store content and SOCE. Although these measurements of global [Ca2+]cyt provide essential information about the functional role of σ1R in the regulation of SOCE, they do not provide detailed information about the effects of σ1R on temporal and spatial aspects of SOCE within the microdomain of the ER-plasma membrane junction. Recently developed, the G-GECO1.2-Orai1 construct encodes for a fully functional Orai1 protein with a genetically encoded fluorescent Ca2+ reporter protein. The Orai1 channel is a key regulator of SOCE. GECO1.2-Orai1 allows for the monitoring of Orai1 channel activity in SOCE microdomains. Within the SOCE microdomains, overexpression of σ1R reduced the frequency of highly-activated G-GECO1.2-Orai1 clusters, which resulted in cumulatively low SOCE. Overexpression of σ1RE102Q, an ALS-causing mutant, failed to inhibit SOCE. In situ, σ1R was shown to interact with another key regulator of SOCE, STIM1 and its less-studied homolog STIM2. Overexpression of σ1R resulted in the inhibition of STIM2.2-mediated SOCE triggered by the ER Ca2+ store depletion. σ1R failed to inhibit STIM2.2-mediated SOCE during basal conditions, suggesting that regulation of SOCE by σ1R requires a greater drop in ER [Ca2+] than occurs under basal conditions.

Subjects/Keywords: RM0301.41 Drug receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Visic, P. (2020). The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains. (Doctoral Dissertation). University of Sussex. Retrieved from http://sro.sussex.ac.uk/id/eprint/90959/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804978

Chicago Manual of Style (16^th Edition):

Visic, Petra. “The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains.” 2020. Doctoral Dissertation, University of Sussex. Accessed March 07, 2021. http://sro.sussex.ac.uk/id/eprint/90959/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804978.

MLA Handbook (7^th Edition):

Visic, Petra. “The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains.” 2020. Web. 07 Mar 2021.

Vancouver:

Visic P. The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains. [Internet] [Doctoral dissertation]. University of Sussex; 2020. [cited 2021 Mar 07]. Available from: http://sro.sussex.ac.uk/id/eprint/90959/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804978.

Council of Science Editors:

Visic P. The role of the Sigma1 receptor (σ1R) in store-operated calcium entry (SOCE) microdomains. [Doctoral Dissertation]. University of Sussex; 2020. Available from: http://sro.sussex.ac.uk/id/eprint/90959/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.804978

University of North Carolina – Greensboro

3. Schmeisser, Marianne G. Creation of a GPR18 homology model using conformational memories.

Degree: 2013, University of North Carolina – Greensboro

URL: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=15054

► G-protein coupled receptors (GPCRs) make up the largest family of eukaryotic membrane receptors, covering a broad range of cellular responses in the body. This wide… (more)

▼ G-protein coupled receptors (GPCRs) make up the largest family of eukaryotic membrane receptors, covering a broad range of cellular responses in the body. This wide range of activity makes them important pharmacological targets. In general, all Class A GPCRs share a common structure that consists of seven transmembrane alpha helices, connected by extracellular and intracellular loops, an extracellular N-terminus, and an intracellular C-terminus. These similarities can be used to construct a model of an unknown receptor, which can then be used to help guide further studies of this receptor and its pharmacology. The orphan GPCR GPR18 is a member of the Class A subfamily of GPCRs. GPR18 binds both lipid-like and small molecule ligands, such as NAGly and abnormal-cannabidiol (Abn-CBD), leading to belief that GPR18 may be the Abnormal Cannabinoid Receptor. The goal of this project was to construct a model of GPR18 in its inactive state and to explore the binding site of a key antagonist already identified for this receptor. A model of the GPR18 inactive (R) state was created using the μ-Opioid receptor (MOR) crystal structure as template (PDB: 4DKL). The Monte Carlo/simulated annealing method, Conformational Memories (CM) was used to study the accessible conformations of three GPR18 transmembrane helices (TMHs) with important sequence divergences from the MOR template: TMH3, TMH4, and TMH7. CM was also used to calculate the accessible conformations for TMH6, which allowed the choice of TMH6 conformers appropriate for the GPR18 R and R* models. Docking studies were guided by the hypothesis that a positively charged residue (either R2.60 or R5.42) may be the primary ligand interaction site in the GPR18 binding pocket. The binding pocket of the antagonist, cannabidiol (CBD) was explored in the inactive state GPR18 model using Glide, an automatic docking program in the Schrödinger modeling suite. These studies identified that both of these argenines are the primary interaction site for CBD. With the pocket determined, extracellular and intracellular loops were calculated using another Monte Carlo technique, Modeler. Once loops were attached, the N and C termini were modeled and added as well. Much like the S1PR1 receptor, and continuing the hypothesis that GPR18 used a lipid level access to the binding pocket, the N terminus displayed a small helical portion that lay atop the bundle, effectively blocking the extracellular side along with EC2. With the identification of key residues and a complete bundle, further mutation studies and dynamic simulations can be used to further refine and test these modeling results.; Molecular Modelling Advisors/Committee Members: Patricia Reggio (advisor).

Subjects/Keywords: G proteins; Drug receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schmeisser, M. G. (2013). Creation of a GPR18 homology model using conformational memories. (Masters Thesis). University of North Carolina – Greensboro. Retrieved from http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=15054

Chicago Manual of Style (16^th Edition):

Schmeisser, Marianne G. “Creation of a GPR18 homology model using conformational memories.” 2013. Masters Thesis, University of North Carolina – Greensboro. Accessed March 07, 2021. http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=15054.

MLA Handbook (7^th Edition):

Schmeisser, Marianne G. “Creation of a GPR18 homology model using conformational memories.” 2013. Web. 07 Mar 2021.

Vancouver:

Schmeisser MG. Creation of a GPR18 homology model using conformational memories. [Internet] [Masters thesis]. University of North Carolina – Greensboro; 2013. [cited 2021 Mar 07]. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=15054.

Council of Science Editors:

Schmeisser MG. Creation of a GPR18 homology model using conformational memories. [Masters Thesis]. University of North Carolina – Greensboro; 2013. Available from: http://libres.uncg.edu/ir/listing.aspx?styp=ti&id=15054

4. NC DOCKS at The University of North Carolina at Greensboro; Schmeisser, Marianne G. Creation of a GPR18 homology model using conformational memories.

Degree: 2013, NC Docks

URL: http://libres.uncg.edu/ir/uncg/f/Schmeisser_uncg_0154M_11272.pdf

► G-protein coupled receptors (GPCRs) make up the largest family of eukaryotic membrane receptors, covering a broad range of cellular responses in the body. This wide… (more)

▼ G-protein coupled receptors (GPCRs) make up the largest family of eukaryotic membrane receptors, covering a broad range of cellular responses in the body. This wide range of activity makes them important pharmacological targets. In general, all Class A GPCRs share a common structure that consists of seven transmembrane alpha helices, connected by extracellular and intracellular loops, an extracellular N-terminus, and an intracellular C-terminus. These similarities can be used to construct a model of an unknown receptor, which can then be used to help guide further studies of this receptor and its pharmacology. The orphan GPCR GPR18 is a member of the Class A subfamily of GPCRs. GPR18 binds both lipid-like and small molecule ligands, such as NAGly and abnormal-cannabidiol (Abn-CBD), leading to belief that GPR18 may be the Abnormal Cannabinoid Receptor. The goal of this project was to construct a model of GPR18 in its inactive state and to explore the binding site of a key antagonist already identified for this receptor. A model of the GPR18 inactive (R) state was created using the μ-Opioid receptor (MOR) crystal structure as template (PDB: 4DKL). The Monte Carlo/simulated annealing method, Conformational Memories (CM) was used to study the accessible conformations of three GPR18 transmembrane helices (TMHs) with important sequence divergences from the MOR template: TMH3, TMH4, and TMH7. CM was also used to calculate the accessible conformations for TMH6, which allowed the choice of TMH6 conformers appropriate for the GPR18 R and R* models. Docking studies were guided by the hypothesis that a positively charged residue (either R2.60 or R5.42) may be the primary ligand interaction site in the GPR18 binding pocket. The binding pocket of the antagonist, cannabidiol (CBD) was explored in the inactive state GPR18 model using Glide, an automatic docking program in the Schrödinger modeling suite. These studies identified that both of these argenines are the primary interaction site for CBD. With the pocket determined, extracellular and intracellular loops were calculated using another Monte Carlo technique, Modeler. Once loops were attached, the N and C termini were modeled and added as well. Much like the S1PR1 receptor, and continuing the hypothesis that GPR18 used a lipid level access to the binding pocket, the N terminus displayed a small helical portion that lay atop the bundle, effectively blocking the extracellular side along with EC2. With the identification of key residues and a complete bundle, further mutation studies and dynamic simulations can be used to further refine and test these modeling results.

Subjects/Keywords: G proteins; Drug receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

NC DOCKS at The University of North Carolina at Greensboro; Schmeisser, M. G. (2013). Creation of a GPR18 homology model using conformational memories. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/uncg/f/Schmeisser_uncg_0154M_11272.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

NC DOCKS at The University of North Carolina at Greensboro; Schmeisser, Marianne G. “Creation of a GPR18 homology model using conformational memories.” 2013. Thesis, NC Docks. Accessed March 07, 2021. http://libres.uncg.edu/ir/uncg/f/Schmeisser_uncg_0154M_11272.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

NC DOCKS at The University of North Carolina at Greensboro; Schmeisser, Marianne G. “Creation of a GPR18 homology model using conformational memories.” 2013. Web. 07 Mar 2021.

Vancouver:

NC DOCKS at The University of North Carolina at Greensboro; Schmeisser MG. Creation of a GPR18 homology model using conformational memories. [Internet] [Thesis]. NC Docks; 2013. [cited 2021 Mar 07]. Available from: http://libres.uncg.edu/ir/uncg/f/Schmeisser_uncg_0154M_11272.pdf.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

NC DOCKS at The University of North Carolina at Greensboro; Schmeisser MG. Creation of a GPR18 homology model using conformational memories. [Thesis]. NC Docks; 2013. Available from: http://libres.uncg.edu/ir/uncg/f/Schmeisser_uncg_0154M_11272.pdf

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Aberdeen

5. Hay, Elizabeth A. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.

Degree: PhD, 2019, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970690005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774032

► Gene regulatory DNA regions are essential for controlling gene expression and they contain a significant proportion of disease-associated variants. Understanding variation within gene regulatory regions… (more)

▼ Gene regulatory DNA regions are essential for controlling gene expression and they contain a significant proportion of disease-associated variants. Understanding variation within gene regulatory regions may facilitate understanding of disease progression or the development of stratified medicines. The CB1 receptor is involved in controlling many physiological processes such as appetite and reward signalling and has been investigated as a drug target. Differences in response and side effects, however, may indicate that genetic variation within the CB1 receptor gene (CNR1), may need to be investigated to better predict disease and drug efficacy. As disease-associated polymorphisms have been identified in non-coding sequences of CNR1, the aim was to investigate the role of CNR1 regulatory elements and how genetic and epigenetic variation influence their activity. This study identified that the CNR1 promoter is active in primary cell cultures generated from the hypothalamus and dorsal root ganglia (DRGs) of rats and is highly susceptible to CpG methylation in DRGs. Additionally, a highly conserved intronic sequence, ECR1, was disrupted in mice using the CRISPR/Cas9 system. Disruption of ECR1 led to reduced CNR1 expression in the hippocampus but not in the hypothalamus as well as reduced CB1 agonistinduced hypothermia, a reduction in ethanol intake and altered anxiety-like behaviour. The major allele of a SNP within ECR1, permitted CNR1 promoter activity and the minor allele significantly repressed CNR1 promoter activity in hypothalamic and DRG cell cultures. In DRGs, allelic variation within ECR1 altered the response of the CNR1 promoter to the CB1 receptor antagonist/inverse agonist, rimonabant. In conclusion, this study indicates that ECR1 is a tissue specific enhancer and may be involved in regulating physiological processes, and, genetic variation in ECR1 can alter its control of the CNR1 promoter. Overall, this study elucidates possible CNR1 gene regulatory mechanisms, and how genetic and epigenetic variation influences gene regulation.

Subjects/Keywords: Genetic regulation; Cannabinoids; Drug receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hay, E. A. (2019). The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970690005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774032

Chicago Manual of Style (16^th Edition):

Hay, Elizabeth A. “The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.” 2019. Doctoral Dissertation, University of Aberdeen. Accessed March 07, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970690005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774032.

MLA Handbook (7^th Edition):

Hay, Elizabeth A. “The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.” 2019. Web. 07 Mar 2021.

Vancouver:

Hay EA. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. [Internet] [Doctoral dissertation]. University of Aberdeen; 2019. [cited 2021 Mar 07]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970690005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774032.

Council of Science Editors:

Hay EA. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. [Doctoral Dissertation]. University of Aberdeen; 2019. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12152970690005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.774032

University of Aberdeen

6. Cowie, Philip David. Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics.

Degree: PhD, 2014, University of Aberdeen

URL: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153056210005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641466

► Genetic variation within the cannabinoid 1 receptor (CB1R) locus (CNR1) has been repeatedly associated with drug addiction pathologies. Genomic annotation of CNR1 indicates the vast… (more)

▼ Genetic variation within the cannabinoid 1 receptor (CB1R) locus (CNR1) has been repeatedly associated with drug addiction pathologies. Genomic annotation of CNR1 indicates the vast majority of this genetic variation likely results in altered transcriptional regulation of the CNR1 gene as a mechanistic link to the disease phenotype. There is a lack of information describing the regulation of CNR1 transcription and the potential impact of disease-associated variation within the CNR1 locus on its transcriptional regulation. This study investigates the impact of an evolutionary conserved regulatory region of CNR1, termed ECR1, and the disease-associated variation contained within, on the transcriptional activity of the cognate CNR1 promoter region. Reporter assays conducted in primary hippocampal cells demonstrate that CNR1 promoter exhibits variable transcriptional activity during periods of CB1R signalling and cell depolarisation. Coupled to allelic variants of ECR1, the CNR1 promoter shows significant changes in transcriptional activity under resting conditions indicating that disease-associated variation within ECR1 may decrease CNR1 transcription. Further, alleles of ECR1 can drive allele-specific transcriptional responses from the CNR1 promoter during periods of CB1R stimulation and cell depolarisation. The results highlight the potential for disease-associated regulatory variation of the CNR1 locus to create stratified transcriptional responses to specific cell signalling scenarios and putatively to clinical strategies employing pharmacological agents. Furthermore, investigation of DNA-protein interactions at the allelic ECR1 region demonstrate that disease-associated variation within ECR1 alters DNA-protein interactions within the nucleus consistent with a decrease in transcriptional activity in the disease-associated allele variant. Collectively the current work supports the hypothesis that disease-associated variation within the ECR1 regulatory region of the CNR1 locus has the capacity to significantly impact on CNR1 promoter transcriptional activity. It is posited that allele-specific transcriptional effects may have a major impact on the susceptibility of individuals to drug addiction or on responses to clinical pharmacological treatments.

Subjects/Keywords: 610.28; Drug receptors; Genetic transcription; Human genetics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cowie, P. D. (2014). Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics. (Doctoral Dissertation). University of Aberdeen. Retrieved from https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153056210005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641466

Chicago Manual of Style (16^th Edition):

Cowie, Philip David. “Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics.” 2014. Doctoral Dissertation, University of Aberdeen. Accessed March 07, 2021. https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153056210005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641466.

MLA Handbook (7^th Edition):

Cowie, Philip David. “Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics.” 2014. Web. 07 Mar 2021.

Vancouver:

Cowie PD. Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics. [Internet] [Doctoral dissertation]. University of Aberdeen; 2014. [cited 2021 Mar 07]. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153056210005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641466.

Council of Science Editors:

Cowie PD. Analysis of the effects of disease-associated variation within a cis-regulatory element of the CNR1 locus on CNR1 promoter dynamics. [Doctoral Dissertation]. University of Aberdeen; 2014. Available from: https://abdn.alma.exlibrisgroup.com/view/delivery/44ABE_INST/12153056210005941 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.641466

University of British Columbia

7. Hughson, Richard Lee. A structural characteriztion of the dog myocardial adrenergic receptors.

Degree: MS- MSc, Physiology, 1973, University of British Columbia

URL: http://hdl.handle.net/2429/32883

► The chronotropic and inotropic responses to isoprenaline and salbutamol were determined in the chloralose anaesthetized dog. The myocardium was denervated, sympathetically and parasympathetically to prevent… (more)

▼ The chronotropic and inotropic responses to isoprenaline and salbutamol were determined in the chloralose anaesthetized dog. The myocardium was denervated, sympathetically and parasympathetically to prevent direct neural influence on the heart rate and myocardial contractility. The heart rate was determined from the E.C.G. Myocardial contractility was indicated by the change in the maximum rate of rise of left ventricular pressure (dP/dt max) at a constant electrically paced heart rate. The structure-activity relationships for salbutamol and isoprenaline were determined from dose-response curves and by plotting the change in contractility (ΔdP/dt max) against the change in heart rate (ΔHR). The data obtained from this series of experiments indicated that the only difference between the effects of the agonists on the inotropic and chronotropic responses of the myocardium was the lower affinity of salbutamol for the adrenergic receptor as indicated by the 100 times greater concentration required to produce the same response level. Previously reported in vitro studies with the guinea pig atrium and dog papillary muscle had indicated that a smaller inotropic response to salbutamol should have been expected. To test this discrepancy between the present in vivo experimentation, and the previous in vitro work, studies were designed to test the guinea pig atrium and the dog papillary muscle in vitro. The effects of the agonists were studied on the isolated guinea pig atrium in a manner that paralleled the in vivo dog study. With the organ bath at 25°C, the chronotropic response, measured by the change in free contraction rate (ΔR), and the inotropic response, determined from the change in peak tension developed (ΔT) during electrical stimulation at 2 Hz, to a single randomly ordered dose of salbutamol or isoprenaline were determined. Salbutamol acted as a partial agonist, that is, had a lower efficacy than isoprenaline. However, the relative effect of each drug on the inotropic and chronotropic responses was almost identical. In the isolated dog papillary muscle, salbutamol displayed a much lower efficacy, producing only 20% of the maximum isoprenaline increase in peak tension developed to the cummulative addition of agonist. The affinity of salbutamol for the adrenergic receptor in this preparation was much lower than that observed in vivo when compared with isoprenaline, 5,000:1 and 100:1 respectively. The structure-activity relationships for salbutamol and isoprenaline showed that the relative effects of these agonists on the in vivo denervated dog myocardial inotropic and chronotropic responses were similar. This observation indicates that the adrenergic receptors of the dog myocardium mediating the inotropic and chronotropic responses are structurally similar at a site complementary to the phenyl ring of the agonist molecule. However,, a definite conclusion regarding the adrenergic receptors responsible for the inotropic response cannot be made because of the unexplained difference in inotropic response observed…

Subjects/Keywords: Adrenergic mechanisms; Drug receptors; Receptors, Adrenergic

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hughson, R. L. (1973). A structural characteriztion of the dog myocardial adrenergic receptors. (Masters Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/32883

Chicago Manual of Style (16^th Edition):

Hughson, Richard Lee. “A structural characteriztion of the dog myocardial adrenergic receptors.” 1973. Masters Thesis, University of British Columbia. Accessed March 07, 2021. http://hdl.handle.net/2429/32883.

MLA Handbook (7^th Edition):

Hughson, Richard Lee. “A structural characteriztion of the dog myocardial adrenergic receptors.” 1973. Web. 07 Mar 2021.

Vancouver:

Hughson RL. A structural characteriztion of the dog myocardial adrenergic receptors. [Internet] [Masters thesis]. University of British Columbia; 1973. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2429/32883.

Council of Science Editors:

Hughson RL. A structural characteriztion of the dog myocardial adrenergic receptors. [Masters Thesis]. University of British Columbia; 1973. Available from: http://hdl.handle.net/2429/32883

Northeastern University

8. Duggirala, Vasantha. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.

Degree: MS, School of Pharmacy, 2014, Northeastern University

URL: http://hdl.handle.net/2047/D20196780

► α7-nicotinic acetylcholine receptor (nAChRs), members of ligand-gated ion channels are becoming attractive targets considering their therapeutic potential for the treatment of cognitive deficits associated with… (more)

▼ α7-nicotinic acetylcholine receptor (nAChRs), members of ligand-gated ion channels are becoming attractive targets considering their therapeutic potential for the treatment of cognitive deficits associated with schizophrenia, Alzheimer's Disease (AD), Parkinson's disease, and attention-deficit/hyperactivity disorders (ADHD), as well as inflammation and neuropathic pain. α7 nAChRs can be activated either by ligands binding at orthosteric site or allosteric site/s along with enhancing the agonist evoked response. But, activation via orthosteric site caused rapid desensitization of the receptors upon exposure to agonist for prolonged time, also under diseased condition like AD the endogenous cholinergic tone is reduced. As an alternative approach, allosteric potentiators are being emphasized. These allosteric ligands regulate nicotinic cholinergic neurotransmission either in a positive or a negative way by binding to a site distinct from orthosteric site. Some of them only potentiate agonist-evoked responses (Type I) while others potentiate responses as well as decrease desensitization kinetics of the receptors (Type II). Among the Type II positive allosteric modulators (PAMs) of α7 nAChRs, 4BP-TQS (4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide) was found to have unique allosteric agonist activity in addition to being a potent PAM. It increased the scope of allosteric approach to a higher level. But with the lack of knowledge about structural features of ligand-receptor binding site, it is difficult to design potent and efficacious ligands. Mechanism of action, location of binding site and amino acids interacting at the site are all under question. As the α7 crystal structure is not available, alternative methods are being considered to discover the structural features. One of the most reliable alternatives being the use of covalent probes, this approach was taken ahead using 4BP-TQS scaffold. Covalent probes can be derived by incorporating reactive groups at the judiciously selected positions of the allosteric ligands to help determine the amino acids involved in the binding of the molecule and their role in the activity can be deduced. Photoreactive groups such as a azido or trifluoromethyl diazirine as well as electrophilic groups such as isothiocyanate were incorporated at the para-position to the phenyl ring of 4BP-TQS which was demonstrated to be a critical position for ago-PAM activity. Identifying key amino acids would aid in mapping the allosteric binding site of 7 nAChRs. Radio-labeled ligands have always been effective tools in understanding ligand-receptor interactions like binding, affinity, etc. Radio-labelled ligands at orthosteric site have been developed and successfully used in research based on acetylcholine receptor binding protein's crystal structure. In this work, I have also synthesized a radioiodinated analog (¹²⁵I) of the active enantiomer (GAT164) of 4IPTQS, a potent ago-PAM of a7 nAChR to study the drug-receptor binding interactions at this distinct…

Subjects/Keywords: alpha7-nicotinic acetylcholine receptor; covalent probe; drug-receptor; Nicotinic receptors; Therapeutic use; Molecular probes; Allosteric regulation; Ligands; Drug receptors; Amino acids

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Duggirala, V. (2014). Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. (Masters Thesis). Northeastern University. Retrieved from http://hdl.handle.net/2047/D20196780

Chicago Manual of Style (16^th Edition):

Duggirala, Vasantha. “Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.” 2014. Masters Thesis, Northeastern University. Accessed March 07, 2021. http://hdl.handle.net/2047/D20196780.

MLA Handbook (7^th Edition):

Duggirala, Vasantha. “Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s.” 2014. Web. 07 Mar 2021.

Vancouver:

Duggirala V. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. [Internet] [Masters thesis]. Northeastern University; 2014. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2047/D20196780.

Council of Science Editors:

Duggirala V. Novel covalent probes for mapping α7 nicotinic acetylcholine receptor allosteric site/s; Novel covalent probes for mapping alpha7 nicotinic acetylcholine receptor allosteric site/s. [Masters Thesis]. Northeastern University; 2014. Available from: http://hdl.handle.net/2047/D20196780

University of Florida

9. Muehlmann, Amber Marie. Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior.

Degree: MS, Medical Sciences - Clinical Investigation (IDP), 2013, University of Florida

URL: https://ufdc.ufl.edu/UFE0046338

► Restricted repetitive behaviors are extremely common in neurodevelopmental disorders. The deer mouse model of repetitive behavior is a particularly useful animal model because repetitive behavior… (more)

Subjects/Keywords: Agonists; Autistic disorder; Dopamine antagonists; Drug combinations; Drug delivery systems; Injections; Medication administration; Modulators; Neurons; Receptors; behavior – heteromeric – receptors – repetitive – stereotypy

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Muehlmann, A. M. (2013). Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior. (Masters Thesis). University of Florida. Retrieved from https://ufdc.ufl.edu/UFE0046338

Chicago Manual of Style (16^th Edition):

Muehlmann, Amber Marie. “Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior.” 2013. Masters Thesis, University of Florida. Accessed March 07, 2021. https://ufdc.ufl.edu/UFE0046338.

MLA Handbook (7^th Edition):

Muehlmann, Amber Marie. “Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior.” 2013. Web. 07 Mar 2021.

Vancouver:

Muehlmann AM. Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior. [Internet] [Masters thesis]. University of Florida; 2013. [cited 2021 Mar 07]. Available from: https://ufdc.ufl.edu/UFE0046338.

Council of Science Editors:

Muehlmann AM. Targeting Adenosine, Dopamine, and Glutamate Heteromeric Receptor Complexes to Treat Restricted, Repetitive Behavior. [Masters Thesis]. University of Florida; 2013. Available from: https://ufdc.ufl.edu/UFE0046338

Macquarie University

10. Salazar Estrada, Ivan de Jesus. Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network.

Degree: 2019, Macquarie University

URL: http://hdl.handle.net/1959.14/1271413

►

Empirical thesis.

Chapter 1. Introduction : EGFR signaling network and targeted therapies – Chapter 2. Design and synthesis of chemical probes targeting EGFR – Chapter… (more)

▼

Empirical thesis.

Chapter 1. Introduction : EGFR signaling network and targeted therapies – Chapter 2. Design and synthesis of chemical probes targeting EGFR – Chapter 3. Reverse chemical proteomics with a non-covalent EGFR-directed proben – Chapter 4. Forward chemical proteomics studies with covalent EGFR probes – Chapter 5. Conclusions and future directions – Appendices.

The epidermal growth factor receptor (EGFR) kinase is a prototypical receptor kinase with critical function in normal homeostasis and disease progression. Eight EGFR inhibitors spanning three generations are FDA-approved for a few types of cancers and ultimately limited by resistance. Drug resistance has recently been associated to EGFR roles beyond its kinase activity and dependent on subcellular localization. Elucidating endogenous EGFR signaling characteristics may lead to more efficacious therapies.

In this thesis work we report the design and synthesis of EGFR-directed probes for taking a chemical proteomics approach to finding potential protein partners of EGFR in the cell. The probes were based on selective EGFR inhibitors and designed to covalently label a lysine residue in the solvent-exposed region of EGFR. Several trifunctional linkers for the modification of other drugs were also obtained. In reverse chemical proteomics using human cDNA libraries from various cancer cells, DNA topoisomerase I was identified as a potential target of the EGFR inhibitor Gefitinib, supporting recent hypothesis of EGFR-topoisomerase crosstalk in drug resistance. In forward chemical proteomics studies in MDA-MB-468 cells, several ATP-utilizing enzymes were identified as potential EGFR interactors. These proteins may in the future be further investigated to validate their interactions with EGFR and understand the biological roles of these interactions to assist the development of new combination therapies.

1 online resource (xviii, 207 pages) illustrations (some colour)

Advisors/Committee Members: Macquarie University. Department of Molecular Sciences.

Subjects/Keywords: Epidermal growth factor; Drug receptors; Chemical inhibitors; EGFR; chemical proteomics; kinase inhibitors; drug resistance

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Salazar Estrada, I. d. J. (2019). Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network. (Doctoral Dissertation). Macquarie University. Retrieved from http://hdl.handle.net/1959.14/1271413

Chicago Manual of Style (16^th Edition):

Salazar Estrada, Ivan de Jesus. “Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network.” 2019. Doctoral Dissertation, Macquarie University. Accessed March 07, 2021. http://hdl.handle.net/1959.14/1271413.

MLA Handbook (7^th Edition):

Salazar Estrada, Ivan de Jesus. “Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network.” 2019. Web. 07 Mar 2021.

Vancouver:

Salazar Estrada IdJ. Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network. [Internet] [Doctoral dissertation]. Macquarie University; 2019. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1959.14/1271413.

Council of Science Editors:

Salazar Estrada IdJ. Synthesis of targeted probes for chemical proteomics studies of the EGFR signaling network. [Doctoral Dissertation]. Macquarie University; 2019. Available from: http://hdl.handle.net/1959.14/1271413

Victoria University of Wellington

11. Jones, Karen. Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure.

Degree: 2009, Victoria University of Wellington

URL: http://hdl.handle.net/10063/1231

► Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three… (more)

▼ Rationale: Following repeated +/-3,4- methylenedioxymethamphetamine (MDMA) administration there is tolerance to many behavioural effects and deficits in serotonergic neurotransmission. Objectives: The present studies had three main objectives. 1. To develop a behavioural assay to examine the effects of acute and repeated MDMA exposure. 2. To use this behavioural assay to determine whether functional changes in serotonin (5-HT)2a or 5-HT2c receptors accompany tolerance to the effects of MDMA. 3. To attempt to reverse behavioural tolerance and 5-HT deficits by administering a treatment that has been shown to desensitise the 5-HT1a autoreceptor. Methods: In separate groups of rats the dose effect curves for MDMAproduced hyperactivity were determined (0.0, 1.0, 3.3, 10.0 mg/kg). In additional groups the effect of MDMA pretreatment (4 X 10mg/kg MDMA injections at 2 hour intervals) or saline vehicle on MDMA-produced hyperactivity was assessed. To determine the experimental parameters for MDMA effects in the Emergence Test (ET) separate groups of rats received MDMA (0.0, 3.3 mg/kg) and were either habituated to a hide box for various periods (15, 30, 45mins) or exposed to the test arena 3 times over a period of days (day 1, 5, 9) or injected daily in the home cage with MDMA (0.0, 3.3mg/kg) for 3 days. Emergence latency following injections of MDMA (0.0, 3.3mg/kg), the 5-HT2a /c agonistm-CPP (0.0, 0.3, 0.6 or 1.25 m/kg), the 5-HT releasing stimulant, fenfluramine (0.0, 1.0, 2.0 mg/kg), and the 5-HT2a agonist DOI (0.0, 1.0, 2.0 mg/kg) was measured. The role of 5-HT2c receptors was assessed by determining the effect of the 5-HT2c antagonist, RS102221 (0.0, 0.25, 0.5, 1.0 mg/kg). The effect of MDMA pretreatment on MDMA (0.0, 3.3 mg/kg), m-CPP (1.25 mg/kg), or fenfluramine (2.0mg/kg) induced increases in emergence latency was also assessed. The functional status of the 5-HT1a autoreceptor following MDMA pretreatment was determined by measuring the effect of the 5-HT1a agonist, 8- OHDPAT (0.0, 0.315, 0.0625, 0.125, 0.25, 0.5 mg/kg, SC), on body temperature. The ability of the 5-HT1a antagonist, WAY100635 (0.0, 0.01, 0.1, 1.0mg/kg, SC, 1 X daily for 7 days or by local injection of 0.0 or 500 ng into the dorsal raphe) to reverse the attenuation of MDMA-induced hyperactivity following MDMA pretreatment was examined. Effects of various treatments on tissue levels of 5-HT and 5-HIAA were also measured using HPLC with EC. Results: MDMA produced dose-dependent hyperactivity and tolerance was produced by MDMA pretreatment. MDMA (3.3mg/kg) increased emergence latency following a 30 minute habituation period and this effect was reduced in MDMA-pretreated rats. Fenfluramine and m-CPP but not DOI also increased emergence latency in a dose-dependent manner. RS102221 dose dependently blocked the acute effects of MDMA and m-CPP. Two weeks following MDMA pretreatment rats were tolerant to the effects of MDMA and fenfluramine, but not m-CPP. MDMA pretreatment also produced significant reductions in tissue levels of 5-HT and 5-HIAA. Subcutaneous… Advisors/Committee Members: Schenk, Susan, Hunt, Maree.

Subjects/Keywords: Ecstasy(drug); Methylenedioxymethamphetamine; Serotonin receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Jones, K. (2009). Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure. (Doctoral Dissertation). Victoria University of Wellington. Retrieved from http://hdl.handle.net/10063/1231

Chicago Manual of Style (16^th Edition):

Jones, Karen. “Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure.” 2009. Doctoral Dissertation, Victoria University of Wellington. Accessed March 07, 2021. http://hdl.handle.net/10063/1231.

MLA Handbook (7^th Edition):

Jones, Karen. “Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure.” 2009. Web. 07 Mar 2021.

Vancouver:

Jones K. Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure. [Internet] [Doctoral dissertation]. Victoria University of Wellington; 2009. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10063/1231.

Council of Science Editors:

Jones K. Tolerance to the Behavioural and Neurochemical Effects of MDMA Following Repeated Exposure. [Doctoral Dissertation]. Victoria University of Wellington; 2009. Available from: http://hdl.handle.net/10063/1231

12. Zeng, Binqui. Flexible ditopic receptors.

Degree: Department of Chemistry, 2017, University of Victoria

URL: http://hdl.handle.net/1828/8227

► This thesis comprises three parts united by a single theme: development of flexible ditopic receptors. In part 1, two bis(crown ether)s were synthesized and their… (more)

▼ This thesis comprises three parts united by a single theme: development of flexible ditopic receptors. In part 1, two bis(crown ether)s were synthesized and their binding selectivities with alkali, alkaline earth and α,ω-primaryalkylidenediammonium cations were studied by electrospray ionization mass spectrometry (ESI-MS). First, we confirmed that the ion intensities of complexes in the gas phase are linearly related to the concentrations of complexes in solution for single crown ether dicarboxylic acid. Binding selectivities of complex bis(crown ether)s with mixtures of alkali cations and with mixtures of alkaline earth cations were then determined directly from ESI-MS spectra. The results from ESIMS are consistent with literature data if ions of like charge and similar type are compared (e. g., among the alkali metals). The stoichiometries of complexes in solution were also probed. Complexes with up to two K⁺ per crown ether were detected by ESI-MS. The research shows that ESI-MS provides an effective tool to study complexation by structurally complex molecules in solution. From the ESI-MS results, bis(crown ether) bolaamphiphiles were designed and synthesized as cation-recognition based membrane-disruption agents. Three bis(crown ether)s were obtained by capping an 18-crown-6 dicarboxylate anhydride with different lengthes of α,ω-alkanedicarboxylic acids extended as the 3-amino-1-propyl esters. Their membrane disrupting activities were explored using vesicle encapsulated 5(6)- carboxyfluorescein (CF) by a fluorescence self-quenching (FSQ) method. The membrane disrupting activity is significantly and specifically enhanced specifically by the addition Sr²⁺ or Ba²⁺ in solution. The membrane-disrupting activity is also enhanced with a increased aliphatic loop length of the starting α,ω-alkanedicarboxylic acid. Based on the mechanism studies of Regen and work conducted in this thesis, we propose that the active form for membrane-disruption is created by a U-shaped sandwich complex between Ba²⁺ and the bis(crown ether) bolaamphiphiles which interacts only with the outer leaflet of the vesicle bilayer. In part 3, a photoswitchable bis(crown ether) based on thioindigo was designed and synthesized as a cation- and photo-regulated membrane-disruption agent. The bis(crown ether) was prepared by capping an 18-crown-6 dicarboxylate anhydride with 7,7’-thioindigo dicarboxylic acid extended as the 8-amino-1-octanyl esters. There is significant difference in the membrane-disrupting activities of the cis- (U-shape) and trans- (S-shape) isomers using the vesicle entrapped CF (FSQ) method. Alkaline earth cations suppress the cis-to-trans thermal isomerization and stabilize the cis-isomers of the 7,7’- thioindigo bis(crown ether) in organic solvent. The results confirm the mechanism proposed, namely, that a U-shaped conformation is required for membrane disruption, that the bis(crown ether)s form sandwich complexes with alkaline earth metal ions. Advisors/Committee Members: Fyles, Thomas M. (supervisor).

Subjects/Keywords: Ion channels; Drug receptors

…signal amplification (transduction).^ Ditopic receptors contain two binding sites… …simultaneous or successive participation of two binding subunits in ditopic receptors may bring… …written by J. S. Bradshaw and co-workers. Here we only focus on ditopic receptors, mostly bis… …ditopic receptors with unusual applications which require cooperative binding. The systems to be… …is only to review briefly photoisomerizable ditopic receptors. Among photoswitchable…

1 more image…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zeng, B. (2017). Flexible ditopic receptors. (Thesis). University of Victoria. Retrieved from http://hdl.handle.net/1828/8227

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zeng, Binqui. “Flexible ditopic receptors.” 2017. Thesis, University of Victoria. Accessed March 07, 2021. http://hdl.handle.net/1828/8227.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zeng, Binqui. “Flexible ditopic receptors.” 2017. Web. 07 Mar 2021.

Vancouver:

Zeng B. Flexible ditopic receptors. [Internet] [Thesis]. University of Victoria; 2017. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1828/8227.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zeng B. Flexible ditopic receptors. [Thesis]. University of Victoria; 2017. Available from: http://hdl.handle.net/1828/8227

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Nova

13. Monteiro, Teresa Maria de Castro Cunha Alves. Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento.

Degree: 2011, Universidade Nova

URL: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6254

► Resumo: O corpo carotídeo gera o quimiorreflexo à hipoxia, tendo por objectivo principal a homeostase dos gases do sangue. Esta tese testou a hipótese da… (more)

▼ Resumo: O corpo carotídeo gera o quimiorreflexo à hipoxia, tendo por objectivo principal a homeostase dos gases do sangue. Esta tese testou a hipótese da função destes quimiossensores não se deteriorar ao longo da idade. In vivo, em ratos anestesiados, foram estudados os efeitos da idade nas respostas cardiorespiratórias a dois tipos de estímulos diferentes: a isquemia carotídea e a manipulação farmacológica de dois neurotransmissores com efeitos opostos nos quimiorreceptores, a adenosina e a dopamina. O modelo de isquemia carotídea corresponde à oclusão bilateral da artéria carótida comum, durante períodos de 5 a 15 s, o que determina um efeito excitatório na ventilação que é abolido pela secção bilateral dos nervos do seio carotídeo. No estudo farmacológico foram analisadas as respostas cardio-respiratórias à adenosina e à dopamina exógenas na presença e na ausência de antagonistas selectivos para os receptores A2A e D2, respectivamente. In vitro, no corpo carotídeo, foi quantificado o efeito de diferentes concentrações de oxigénio no conteúdo do segundo mensageiro comum à activação dos receptores A2A e D2, o cAMP. Em conjunto, estes resultados demonstraram que no rato o controlo da ventilação pelo corpo carotídeo se mantém inalterado ao longo da idade. – – – – – – – ABSTRACT: The carotid body initiates reflexes aimed principally at the homeostatic maintenance of blood gas tensions. This thesis tested the hypothesis of the function of these quimiossensores not deteriorate through age. In vivo, in anesthetized rats, we studied the effects of age on cardiorespiratory responses to two different types of stimuli: carotid ischemia and pharmacological manipulation of neurotransmitters with two opposite effects on chemoreceptors, adenosine and dopamine. The model of carotid ischemia corresponded to bilateral occlusion of common carotid artery, during periods of 5 to 15 s, which determines an excitatory effect on ventilation that is abolished by bilateral section of carotid sinus nerve. The pharmacological study analyzed the cardiorespiratory responses to exogenous adenosine and dopamine in the presence and absence of selective antagonists for the A2A and D2 receptors, respectively. In vitro, at the carotid body, it was quantified the effect of different concentrations of oxygen in the content of the common second messenger for the activation of A2A and D2 receptors, the cAMP. Together, these results showed that in rats the control of ventilation by carotid body remains unchanged through age. Advisors/Committee Members: Monteiro, Maria Emília.

Subjects/Keywords: Carotid Body; Receptors, Neurotransmitter - drug effects; Aging; Animal Experimentation; Rats; Farmacologia

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Monteiro, T. M. d. C. C. A. (2011). Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento. (Thesis). Universidade Nova. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6254

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Monteiro, Teresa Maria de Castro Cunha Alves. “Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento.” 2011. Thesis, Universidade Nova. Accessed March 07, 2021. http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6254.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Monteiro, Teresa Maria de Castro Cunha Alves. “Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento.” 2011. Web. 07 Mar 2021.

Vancouver:

Monteiro TMdCCA. Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento. [Internet] [Thesis]. Universidade Nova; 2011. [cited 2021 Mar 07]. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6254.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Monteiro TMdCCA. Avaliação funcional e farmacológica do corpo carotídeo do rato no envelhecimento. [Thesis]. Universidade Nova; 2011. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/6254

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

14. Khaled, Maram Ahmed Taha Mohamed. The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour.

Degree: 2011, University of Toronto

URL: http://hdl.handle.net/1807/29570

►

Dopamine D3 receptors (DRD3) are implicated in relapse to drugs. The current study investigated the role of DRD3 in cue-induced reinstatement of nicotine-seeking in rats.… (more)

Subjects/Keywords: dopamine D3 receptors; addiction; brain; drug discovery; motivation; 0419

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Khaled, M. A. T. M. (2011). The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/29570

Chicago Manual of Style (16^th Edition):

Khaled, Maram Ahmed Taha Mohamed. “The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour.” 2011. Masters Thesis, University of Toronto. Accessed March 07, 2021. http://hdl.handle.net/1807/29570.

MLA Handbook (7^th Edition):

Khaled, Maram Ahmed Taha Mohamed. “The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour.” 2011. Web. 07 Mar 2021.

Vancouver:

Khaled MATM. The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour. [Internet] [Masters thesis]. University of Toronto; 2011. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1807/29570.

Council of Science Editors:

Khaled MATM. The Role of the Dopamine D, Receptors in Cue-induced Reinstatement of Nicotine-seeking Behaviour. [Masters Thesis]. University of Toronto; 2011. Available from: http://hdl.handle.net/1807/29570

University of Aberdeen

15. Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine, Medical Sciences and Nutrition.; Medical Research Scotland. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.

Degree: School of Medicine, Medical Sciences and Nutrition., 2019, University of Aberdeen

URL: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=241466 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=241466&custom_att_2=simple_viewer

Subjects/Keywords: Genetic regulation.; Cannabinoids.; Drug receptors.

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine, M. S. a. N. ;. M. R. S. (2019). The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. (Doctoral Dissertation). University of Aberdeen. Retrieved from http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=241466 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=241466&custom_att_2=simple_viewer

Chicago Manual of Style (16^th Edition):

Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine, Medical Sciences and Nutrition ; Medical Research Scotland. “The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.” 2019. Doctoral Dissertation, University of Aberdeen. Accessed March 07, 2021. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=241466 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=241466&custom_att_2=simple_viewer.

MLA Handbook (7^th Edition):

Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine, Medical Sciences and Nutrition ; Medical Research Scotland. “The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy.” 2019. Web. 07 Mar 2021.

Vancouver:

Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine MSaN;MRS. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. [Internet] [Doctoral dissertation]. University of Aberdeen; 2019. [cited 2021 Mar 07]. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=241466 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=241466&custom_att_2=simple_viewer.

Council of Science Editors:

Hay, Elizabeth A.; MacKenzie, Alasdair.; Pertwee, R. G.(Roger G.); University of Aberdeen.School of Medicine MSaN;MRS. The effects of genetic and epigenetic variation on the control of the cannabinoid-1 receptor gene and their role in disease and drug efficacy. [Doctoral Dissertation]. University of Aberdeen; 2019. Available from: http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=241466 ; http://digitool.abdn.ac.uk:1801/webclient/DeliveryManager?pid=241466&custom_att_2=simple_viewer

University of Arizona

16. Beaumont, Kevin. Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists .

Degree: 1979, University of Arizona

URL: http://hdl.handle.net/10150/565435

Subjects/Keywords: Drug receptors.; Neurotransmitters.; Huntington's chorea.

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Beaumont, K. (1979). Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/565435

Chicago Manual of Style (16^th Edition):

Beaumont, Kevin. “Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists .” 1979. Doctoral Dissertation, University of Arizona. Accessed March 07, 2021. http://hdl.handle.net/10150/565435.

MLA Handbook (7^th Edition):

Beaumont, Kevin. “Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists .” 1979. Web. 07 Mar 2021.

Vancouver:

Beaumont K. Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists . [Internet] [Doctoral dissertation]. University of Arizona; 1979. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10150/565435.

Council of Science Editors:

Beaumont K. Gamma-aminobutyric acid and glutamic acid in Huntington's Disease: investigation of neurotransmitter receptors using radiolabeled agonists . [Doctoral Dissertation]. University of Arizona; 1979. Available from: http://hdl.handle.net/10150/565435

University of Arizona

17. Wastek, Gregory John, 1947-. NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES .

Degree: 1978, University of Arizona

URL: http://hdl.handle.net/10150/298571

Subjects/Keywords: Drug receptors.; Neurotransmitters.; Huntington's chorea.

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wastek, Gregory John, 1. (1978). NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/298571

Chicago Manual of Style (16^th Edition):

Wastek, Gregory John, 1947-. “NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES .” 1978. Doctoral Dissertation, University of Arizona. Accessed March 07, 2021. http://hdl.handle.net/10150/298571.

MLA Handbook (7^th Edition):

Wastek, Gregory John, 1947-. “NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES .” 1978. Web. 07 Mar 2021.

Vancouver:

Wastek, Gregory John 1. NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES . [Internet] [Doctoral dissertation]. University of Arizona; 1978. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10150/298571.

Council of Science Editors:

Wastek, Gregory John 1. NEUROTRANSMITTER AND RECEPTOR ALTERATIONS IN NEUROPSYCHIATRIC DISEASES . [Doctoral Dissertation]. University of Arizona; 1978. Available from: http://hdl.handle.net/10150/298571

University of British Columbia

18. Polanin, Alicia. Histamine receptors in rabbit atria.

Degree: MS- MSc, Pharmaceutical Sciences, 1979, University of British Columbia

URL: http://hdl.handle.net/2429/22240

► In order to characterize the types of histamine receptors (H₁ or H₂) in rabbit atria, isolated atrial preparations were exposed to selective histamine receptor agonists,… (more)

Subjects/Keywords: Rabbits - physiology; Histamine; Receptors, drug

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Polanin, A. (1979). Histamine receptors in rabbit atria. (Masters Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/22240

Chicago Manual of Style (16^th Edition):

Polanin, Alicia. “Histamine receptors in rabbit atria.” 1979. Masters Thesis, University of British Columbia. Accessed March 07, 2021. http://hdl.handle.net/2429/22240.

MLA Handbook (7^th Edition):

Polanin, Alicia. “Histamine receptors in rabbit atria.” 1979. Web. 07 Mar 2021.

Vancouver:

Polanin A. Histamine receptors in rabbit atria. [Internet] [Masters thesis]. University of British Columbia; 1979. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2429/22240.

Council of Science Editors:

Polanin A. Histamine receptors in rabbit atria. [Masters Thesis]. University of British Columbia; 1979. Available from: http://hdl.handle.net/2429/22240

Freie Universität Berlin

19. Kraus, Larissa. RNA-edited glycine receptors in temporal lobe epilepsy.

Degree: 2020, Freie Universität Berlin

URL: http://dx.doi.org/10.17169/refubium-27016

► C-zu-U RNA-Editierung wurde sowohl als adaptiver als auch maladaptiver Prozess bei Temporallappenepilepsie (TLE) beschrieben. TLE ist die häufigste Form der fokalen Epilepsie, mit einem hohen… (more)

▼ C-zu-U RNA-Editierung wurde sowohl als adaptiver als auch maladaptiver Prozess bei Temporallappenepilepsie (TLE) beschrieben. TLE ist die häufigste Form der fokalen Epilepsie, mit einem hohen Anteil an pharmakoresistenten Verläufen, trotz einer Vielzahl an verfügbaren antiepileptischen Substanzen. Einen neuen potentiell antiepileptischen Mechanismus stellen RNA-editierte Glyzinrezeptoren (edGlyR) dar. Hippocampi von Patienten mit pharmakoresistenter TLE zeigen eine Überexpression von edGlyR mRNA, welche mit der Schwere der Hippocampus-Sklerose korreliert. C-zu-U RNA-Editierung der GlyR mRNA führt zu einem Funktionsgewinn und zu einer erhöhten Affinität für Glyzin. edGlyR wirken überwiegend präsynaptisch, wo sie die Freisetzung von Neurotransmittern erhöhen und bedingt durch die Lokalisation auf inhibitorischen oder exzitatorischen Neuronen zu einer verstärkten oder verminderten neuronalen Erregbarkeit führen. Die C-zu-U RNA-Editierung der GlyR mRNA könnte daher zur Anfallsgenerierung beitragen oder einen adaptiven Mechanismus zur Verringerung der Übererregbarkeit darstellen. Ziel dieser Arbeit war es, spezifische edGlyR-Antagonisten zu identifizieren und ihren Einfluss auf epileptische Aktivität im humanen Gehirn ex vivo zu untersuchen sowie mit Hilfe eines RNA-Editierungssensors das Expressionsmuster von edGlyR auf Einzelzellebene in humanen Hirnschnittkulturen zu identifizieren. Weder mittels high-throughput Screening noch strukturbasierter Datenbankanalyse konnten jedoch in dieser Arbeit spezifische Antagonisten für edGlyR identifiziert werden. Eine der getesteten potentiellen edGlyR Antagonisten, Dimethylethanolamin (DMEA), wurde bereits in diversen präklinischen und klinischen Studien als Therapie für neurologische Erkrankungen getestet, jedoch ohne detailliertes Wissen über den Wirkmechanismus. In dieser Arbeit konnte ich zeigen, dass DMEA die spontane Aktivität von primären neuronalen Kulturen reduziert sowie antiepileptische Effekte in reseziertem humanem Hirngewebe von TLE Patienten aufweist. Zudem konnte ich eine stabile viral-vermittelte Expression des RNA-Editierungssensors spezifisch in Neuronen von humanen Hirnschnittkulturen zeigen. Die Anwendung von DMEA als antiepileptische Substanz sowie die Identifizierung von RNA-Editierung auf Einzelzellenebene stellen essentielle Werkzeuge für die Entwicklung neuartiger antiepileptischer Therapieansätze für Patienten mit pharmakoresistenter TLE dar. Advisors/Committee Members: female (gender), N.N. (firstReferee), N.N. (furtherReferee).

Subjects/Keywords: Epilepsy; Glycine receptors; RNA-editing; drug development; ddc:610

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kraus, L. (2020). RNA-edited glycine receptors in temporal lobe epilepsy. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-27016

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kraus, Larissa. “RNA-edited glycine receptors in temporal lobe epilepsy.” 2020. Thesis, Freie Universität Berlin. Accessed March 07, 2021. http://dx.doi.org/10.17169/refubium-27016.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kraus, Larissa. “RNA-edited glycine receptors in temporal lobe epilepsy.” 2020. Web. 07 Mar 2021.

Vancouver:

Kraus L. RNA-edited glycine receptors in temporal lobe epilepsy. [Internet] [Thesis]. Freie Universität Berlin; 2020. [cited 2021 Mar 07]. Available from: http://dx.doi.org/10.17169/refubium-27016.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kraus L. RNA-edited glycine receptors in temporal lobe epilepsy. [Thesis]. Freie Universität Berlin; 2020. Available from: http://dx.doi.org/10.17169/refubium-27016

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

The Ohio State University

20. Ruffolo, Robert Richard. Biochemical and pharmacological characterization of the alpha-adrenoreceptor.

Degree: PhD, Graduate School, 1976, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1487005384325843

Subjects/Keywords: Health Sciences; Drug receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ruffolo, R. R. (1976). Biochemical and pharmacological characterization of the alpha-adrenoreceptor. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1487005384325843

Chicago Manual of Style (16^th Edition):

Ruffolo, Robert Richard. “Biochemical and pharmacological characterization of the alpha-adrenoreceptor.” 1976. Doctoral Dissertation, The Ohio State University. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487005384325843.

MLA Handbook (7^th Edition):

Ruffolo, Robert Richard. “Biochemical and pharmacological characterization of the alpha-adrenoreceptor.” 1976. Web. 07 Mar 2021.

Vancouver:

Ruffolo RR. Biochemical and pharmacological characterization of the alpha-adrenoreceptor. [Internet] [Doctoral dissertation]. The Ohio State University; 1976. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1487005384325843.

Council of Science Editors:

Ruffolo RR. Biochemical and pharmacological characterization of the alpha-adrenoreceptor. [Doctoral Dissertation]. The Ohio State University; 1976. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1487005384325843

University of Houston

21. Shah, Pranav. Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism.

Degree: Pharmaceutics, Drug Metabolism and Pharmacokinetics, University of Houston

URL: http://hdl.handle.net/10657/3640

► Drug metabolism is affected in various diseases and altered physiological states such as cancer, cardiovascular diseases, diabetes, obesity, liver disorders, etc. The common factor underlying… (more)

▼ Drug metabolism is affected in various diseases and altered physiological states such as cancer, cardiovascular diseases, diabetes, obesity, liver disorders, etc. The common factor underlying all these disease states is inflammation. Accumulating evidence has shown that inflammation can alter the gene expression and activity of several drug metabolizing enzymes and transporters (DMETs) however, the exact mechanism is unknown. Although well established studies have attributed the down-regulation of DMET activities and protein expression to the reduction in their gene expression levels, further research is needed to establish the clinical relevance of this down-regulation. Furthermore, clinical relevance of down-regulation of DMETs during inflammation or pathophysiological conditions needs to be ascertained. Our overall aim is to determine molecular mechanisms that regulate gene expression of DMETs during inflammation and ascertain the clinical relevance of this down-regulation in a mouse model of obesity. Inflammatory responses in the liver are primarily mediated by specific trans-membrane receptors known as Toll-like receptors (TLRs). These receptors are key components of the innate immune response and are present on immune cells as well as hepatocytes in the liver. Out of the 13 known TLRs, we selected TLR2, TLR3 and TLR4 (activated by gram-positive bacterial components, viral components and gram-negative bacterial components, respectively) as they play major roles in immune reactions elicited during various pathophysiological conditions. TLR signaling is mediated by adaptor proteins Toll/interleukin (IL)1 receptor (TIR) domain containing adaptor protein (TIRAP) and TIR domain containing adaptor inducing interferon (IFN)-β (TRIF). We have shown that activation of TLR2 by lipoteichoic acid (LTA) and TLR4 by lipopolysaccharide (LPS) caused down-regulation of gene expression and activity of key hepatic DMETs. This down-regulation was associated with reduced expression of the nuclear receptors, constitutive androstane receptor (CAR) and pregnane X receptor (PXR), which heterodimerize with the central nuclear receptor, retinoid x receptor alpha (RXRα). Our central hypothesis is that drug metabolism is altered by activation of innate immune components and in obesity. We propose to achieve our goals by pursuing the following Specific Aims: Aim 1: To determine the role of the adaptor protein, TRIF down-regulating the gene expression of DMEs and transporters. We hypothesize that the adaptor protein TRIF mediates the down-regulation of DMETs through TLR4 and TLR3. We observed that down-regulation of DMETs on activation of TLR4 and TLR3 is independent of the adaptor protein TRIF. We also found that the MAP kinase, c-Jun-N-terminal kinase (JNK) is involved in mediating the down-regulation of DMET through TLR3 & TLR4. Aim 2: To determine the role of nuclear receptor CAR in TLR2- & 4-mediated down-regulation of DMEs and transporters. We hypothesize that CAR mediates the down-regulation of DMEs and transporters through TLR2 and… Advisors/Committee Members: Ghose, Romi (advisor), Hu, Ming (committee member), Chow, Diana Shu-Lian (committee member), Moorthy, Bhagavatula (committee member), Thevananther, Sundararajah (committee member).

Subjects/Keywords: Toll-like receptors; Nuclear receptors; Obesity; Drug metabolism

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shah, P. (n.d.). Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism. (Doctoral Dissertation). University of Houston. Retrieved from http://hdl.handle.net/10657/3640

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Chicago Manual of Style (16^th Edition):

Shah, Pranav. “Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism.” Doctoral Dissertation, University of Houston. Accessed March 07, 2021. http://hdl.handle.net/10657/3640.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

MLA Handbook (7^th Edition):

Shah, Pranav. “Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism.” Web. 07 Mar 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Shah P. Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism. [Internet] [Doctoral dissertation]. University of Houston; [cited 2021 Mar 07]. Available from: http://hdl.handle.net/10657/3640.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Council of Science Editors:

Shah P. Roles of Toll-Like Receptors, Nuclear Receptors and Obesity in Drug Metabolism. [Doctoral Dissertation]. University of Houston; Available from: http://hdl.handle.net/10657/3640

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Duquesne University

22. Hasan, Mahmud. Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models.

Degree: PhD, Pharmacology, 2020, Duquesne University

URL: https://dsc.duq.edu/etd/1935

► Tamoxifen is a first-generation selective estrogen receptor modulator, which reduces the risk of both invasive and non-invasive breast cancer (BC) as well as tumor… (more)

▼ Tamoxifen is a first-generation selective estrogen receptor modulator, which reduces the risk of both invasive and non-invasive breast cancer (BC) as well as tumor recurrence in several clinical trials. However, chronic use of tamoxifen can increase uterine cancer risk and induce tamoxifen resistance. In past studies, melatonin alone reversed tamoxifen resistance induced by light exposure at night in rodents. This study demonstrates that melatonin or melatonin-based ligands (e.g., melatonin-tamoxifen drug conjugates) may be novel BC therapies that are efficacious and free of side effects. To investigate this further, five melatonin-tamoxifen drug conjugates with different linker sizes were synthesized and screened for their anti-cancer actions in a variety of BC cells that included: MCF-7 (ER+), tamoxifen-resistant MCF-7 (TamR), MMC (HER2+), MDA-MB-231 (triple-negative), and BT-549 (triple-negative). Specifically, their actions against cell viability and migration and binding affinity to MT1 melatonin receptor (MT1Rs) and estrogen receptor 1 (ESR1) were assessed. The melatonin-tamoxifen drug conjugate linked with four (C4) or five (C5) carbons demonstrated the most favorable pharmacological characteristics with respect to potency and efficacy to inhibit BC cell viability and migration. C4 and C5 also exhibited unique binding profiles (affinity for ESR1 and MT1R) compared to the other conjugates. C4 and C5 were further assessed for their actions against tamoxifen-resistant (TamR) MCF-7 cells and patient-derived xenograft triple-negative BC cells (TU-BcX-4IC) as well as for potential mechanisms of action using selective MEK1/2, MEK5, and PI3K inhibitors. C4 and C5 inhibited TamR MCF-7 cells with equal potency and efficacy and both C4 and C5 inhibited TU-BcX-4IC cell viability. Even though both compounds demonstrated similar inhibitory actions against BC cell viability and migration, how this occurred, at a mechanistic level, was quite different between C4 and C5 in the cell lines. The underlying mechanisms of C4 and C5 in BC cell lines were context-specific and involved ERK1/2, ERK5, PI3 kinase, and NF-κB. They also exhibited unique pharmacokinetic profiles, where C4 had higher relative oral bioavailability than C5. These melatonin-tamoxifen drug conjugates show promise as novel anti-BC drugs. Advisors/Committee Members: Paula A. Witt-Enderby, David A. Johnson, Jane E. Cavanaugh, Lauren A. O’Donnell, Robert E. Stratford.

Subjects/Keywords: melatonin-tamoxifen drug conjugates; triple negative breast cancer; tamoxifen resistant breast cancer; MEK1/2; MEK5; PI3 kinase; estrogen receptors; melatonin receptors

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hasan, M. (2020). Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models. (Doctoral Dissertation). Duquesne University. Retrieved from https://dsc.duq.edu/etd/1935

Chicago Manual of Style (16^th Edition):

Hasan, Mahmud. “Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models.” 2020. Doctoral Dissertation, Duquesne University. Accessed March 07, 2021. https://dsc.duq.edu/etd/1935.

MLA Handbook (7^th Edition):

Hasan, Mahmud. “Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models.” 2020. Web. 07 Mar 2021.

Vancouver:

Hasan M. Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models. [Internet] [Doctoral dissertation]. Duquesne University; 2020. [cited 2021 Mar 07]. Available from: https://dsc.duq.edu/etd/1935.

Council of Science Editors:

Hasan M. Melatonin-Tamoxifen Drug Conjugates as Breast Cancer Drugs: Pharmacological Evaluation in Phenotypically Diverse Breast Cancer Models and Pharmacokinetic Assessment in Liver Microsome and Female Mouse Models. [Doctoral Dissertation]. Duquesne University; 2020. Available from: https://dsc.duq.edu/etd/1935

University of Toledo Health Science Campus

23. Lilly, Scott Matthew. Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1.

Degree: PhD, College of Graduate Studies, 2006, University of Toledo Health Science Campus

URL: http://rave.ohiolink.edu/etdc/view?acc_num=mco1145293063

► Chronic FZP treatment induces anticonvulsant tolerance and the expression of a withdrawal syndrome upon drug discontinuation. These behavioral changes are accompanied by selective in vitro… (more)

▼ Chronic FZP treatment induces anticonvulsant tolerance and the expression of a withdrawal syndrome upon drug discontinuation. These behavioral changes are accompanied by selective in vitro alterations in synaptic neurotransmission of the hippocampal CA1 region that, like in vivo manifestations of tolerance and withdrawal, can be pharmacologically reversed with a single exposure to specific receptor antagonists. A candidate mechanism for the coordinate changes in inhibitory and excitatory neurotransmission occurring 2d after cessation of 1-week FZP treatment, is a reduction in membrane-associated PKA activity and PKA-RIIBeta protein, effects that are spatially and temporally consistent with inhibitory and excitatory synaptic alterations (Lilly et al., 2003). Indeed, the functional deficits apparent in GABAA receptors apparent at this time point, which include GABA/benzodiazepine allosteric uncoupling, a decreased in mIPSC amplitude, and a decrease in alpha 1 subunit protein expression, can be accomplished by local reductions in PKA activity. However, AKAP150, the major PKA-RIIBeta scaffolding protein and determinant of membrane-associated PKA activity, is located proximate to excitatory, not inhibitory synapses in rat hippocampal CA1 (Lilly et al., 2005). At these synapses, there is an increase in the expression of GluR1-containing AMPA receptors 2d after cessation of FZP treatment, a finding that implies an alteration in local trafficking of these receptors, for which AKAP150-tethered PKA has been implicated (Lilly et al., 2006). A decrease in AKAP150-tethered PKA activity would favor the 234 dephosphorylation of the AMPA receptor GluR1 subunit on Ser845, and the subsequent internalization of the receptor complex. This interpretation is consistent with the normalization of GluR1-pSer845 at this time point and the subsequent normalization of AMPA receptor synaptic currents. Collectively these studies provide support for the hypothesis that alterations in membrane-associated PKA activity contribute to the acquisition and persistence of GABAA receptor dysfunction, and the impending recovery of normal AMPA receptor function 2d after cessation of chronic FZP treatment. Advisors/Committee Members: Tietz, Ph.D., Elizabeth (Advisor).

Subjects/Keywords: Benzodiapepines; GABAA Receptors; Hippocampus; Drug Tolerance; Drug Dependence; Plasticity

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lilly, S. M. (2006). Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1. (Doctoral Dissertation). University of Toledo Health Science Campus. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=mco1145293063

Chicago Manual of Style (16^th Edition):

Lilly, Scott Matthew. “Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1.” 2006. Doctoral Dissertation, University of Toledo Health Science Campus. Accessed March 07, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=mco1145293063.

MLA Handbook (7^th Edition):

Lilly, Scott Matthew. “Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1.” 2006. Web. 07 Mar 2021.

Vancouver:

Lilly SM. Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1. [Internet] [Doctoral dissertation]. University of Toledo Health Science Campus; 2006. [cited 2021 Mar 07]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1145293063.

Council of Science Editors:

Lilly SM. Protein Kinase A Alterations Following Chronic Flurazepam Treatment: Implications for Inhibitory and Excitatory Synaptic Plasticity in Rat Hippocampal CA1. [Doctoral Dissertation]. University of Toledo Health Science Campus; 2006. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=mco1145293063

University of Alberta

24. Bahaaldin Bagi Zarandi, Batool-Faegheh. Evaluation of 7-OH-DPAT as a DA D3 receptor agonist.

Degree: PhD, Faculty of Pharmacy and Pharmaceutical Sciences, 1998, University of Alberta

URL: https://era.library.ualberta.ca/files/ks65hf29q

Subjects/Keywords: Drug receptors.; Dopamine – Dose-response relationship.

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bahaaldin Bagi Zarandi, B. (1998). Evaluation of 7-OH-DPAT as a DA D3 receptor agonist. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/ks65hf29q

Chicago Manual of Style (16^th Edition):

Bahaaldin Bagi Zarandi, Batool-Faegheh. “Evaluation of 7-OH-DPAT as a DA D3 receptor agonist.” 1998. Doctoral Dissertation, University of Alberta. Accessed March 07, 2021. https://era.library.ualberta.ca/files/ks65hf29q.

MLA Handbook (7^th Edition):

Bahaaldin Bagi Zarandi, Batool-Faegheh. “Evaluation of 7-OH-DPAT as a DA D3 receptor agonist.” 1998. Web. 07 Mar 2021.

Vancouver:

Bahaaldin Bagi Zarandi B. Evaluation of 7-OH-DPAT as a DA D3 receptor agonist. [Internet] [Doctoral dissertation]. University of Alberta; 1998. [cited 2021 Mar 07]. Available from: https://era.library.ualberta.ca/files/ks65hf29q.

Council of Science Editors:

Bahaaldin Bagi Zarandi B. Evaluation of 7-OH-DPAT as a DA D3 receptor agonist. [Doctoral Dissertation]. University of Alberta; 1998. Available from: https://era.library.ualberta.ca/files/ks65hf29q

University of Texas Southwestern Medical Center

25. Schaffer, Nathaniel Elliot. DAF-12: A Novel Drug Target in Parasitic Nematodes.

Degree: 2014, University of Texas Southwestern Medical Center

URL: http://hdl.handle.net/2152.5/6590

► The nuclear receptor DAF-12, first identified in C. elegans, controls nematode species' entry into and exit from metabolically hypoactive resting states. In all of the… (more)

▼ The nuclear receptor DAF-12, first identified in C. elegans, controls nematode species' entry into and exit from metabolically hypoactive resting states. In all of the parasitic species studied thus far, that resting state is the infectious third larval (iL3) stage, and activation of the receptor in iL3 worms outside of the host induces a premature and lethal molt (Wang et al. 2009; Motola et al. 2006). In contrast, the relatively uncontrolled soybean parasite Heterodera glycines, which causes USD 1 billion of crop damage annually in the U.S. (Wrather and Koenning 2006; Davis and Tylka 2005), does not go through an iL3 stage but rather arrests as the preinfectious second juvenile (piJ2) within the egg (Davis and Tylka 2005). However, just as iL3 worms only molt to L4 when they are inside their host (Wang et al. 2009), H. glycines nematodes only hatch as infectious J2s when they are near the plant roots required to support their development (Davis and Tylka 2005). This work demonstrates the importance of the DAF-12 ortholog in H. glycines for regulating hatching and introduces the the first well-defined molecular target for controlling the spread of this important pathogen. Additionally, an ortholog with significant sequence and likely functional similarity is identified in the related parasite Globodera pallida, which causes an identical disease in other major agricultural crops including potato and tomato plants and exhibits the same arrest phenotype inside the egg as H. glycines. Finally, a DAF-12 ortholog is cloned from Onchocerca gutturosa, one of several species in the Onchocerca genus that causes the disease onchocerciasis in both humans and livestock. Importantly, since onchocerciasis continues to elude the eradication efforts of several well-funded international programs, both an existing agonist and an avenue to identify endogenous agonists for the receptor are identified. These studies offer direction for the development of novel therapeutics to control these socially and economically important pathogens. Advisors/Committee Members: Phillips, Margaret A., Mangelsdorf, David J., Kliewer, Steven A., Brown, Michael S., Ranganathan, Rama.

Subjects/Keywords: Antinematodal Agents; Drug Delivery Systems; Helminth Proteins; Nematoda; Receptors, Cytoplasmic and Nuclear

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Schaffer, N. E. (2014). DAF-12: A Novel Drug Target in Parasitic Nematodes. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/6590

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Schaffer, Nathaniel Elliot. “DAF-12: A Novel Drug Target in Parasitic Nematodes.” 2014. Thesis, University of Texas Southwestern Medical Center. Accessed March 07, 2021. http://hdl.handle.net/2152.5/6590.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Schaffer, Nathaniel Elliot. “DAF-12: A Novel Drug Target in Parasitic Nematodes.” 2014. Web. 07 Mar 2021.

Vancouver:

Schaffer NE. DAF-12: A Novel Drug Target in Parasitic Nematodes. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2014. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2152.5/6590.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Schaffer NE. DAF-12: A Novel Drug Target in Parasitic Nematodes. [Thesis]. University of Texas Southwestern Medical Center; 2014. Available from: http://hdl.handle.net/2152.5/6590

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Nova

26. Sousa, Carina Isabel Correia de. Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa.

Degree: 2012, Universidade Nova

URL: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8170

► RESUMO: O maraviroc (MVC) é o único anti-retroviral antagonista do co-receptor CCR5 licenciado e interage com as ansas transmembranares de CCR5, induzindo uma alteração da… (more)

▼ RESUMO: O maraviroc (MVC) é o único anti-retroviral antagonista do co-receptor CCR5 licenciado e interage com as ansas transmembranares de CCR5, induzindo uma alteração da sua conformação e impedindo a interacção com gp120. O MVC é activo apenas contra estirpes R5 de HIV-1, sendo utilizado em terapia de recurso. Neste trabalho, foi estudada a diversidade genética da região C2V3C3 do gene env de estirpes de HIV-1 de oxicodependentes por via endovenosa da Grande Lisboa, pesquisando-se também a presença de polimorfismos genéticos naturais. Foram utilizadas 52 amostras de plasma e para 35 destas foi amplificado por RT-nested PCR um produto de 565 pb. A análise filogenética revelou a seguinte distribuição de genótipos: 23 B (incluindo, provavelmente, 2 CRF14_BG), 8 A, 3 G e 1 F1. Após tradução, e por comparação com a sequência consenso B, verificou-se uma elevada frequência de polimorfismos genéticos, sendo encontradas algumas “assinaturas de aminoácidos” relativas aos subtipos não-B. Realizou-se ainda uma pesquisa de locais de N-glicosilação e a previsão da utilização de co-receptores (abordagem genotípica), com recurso às regras 11/25 e da carga líquida da ansa V3 e aos programas PSSM e geno2pheno[coreceptor]. Observou-se uma conservação genérica do número de locais de N-glicosilação e foram identificadas 5 sequências com tropismo X4 ou duplo. Por fim, com base na literatura, realizou-se uma pesquisa de polimorfismos genéticos associados a resistência ao MVC presentes na ansa V3. Foi observado um número elevado destas mutações. A presença dos padrões 11S+26V e 20F+25D+26V, num total de 3 sequências, é relevante, visto estes estarem inequivocamente associados à resistência in vivo ao MVC. Apesar de não estar ainda definido um perfil de resistência para o MVC, a presença das mutações encontradas, em indivíduos sem contacto prévio com o fármaco, trará implicações relevantes na sua gestão clínica, considerando a introdução do MVC na terapia de recurso. – – – - ABSTRACT: Maraviroc (MVC) is the only CCR5 inhibitor licensed today. This drug interacts with the transmembrane helices of CCR5 co-receptor, inducing a conformation change of its extracellular loops and preventing the interaction with gp120. MVC is only active against R5 strains of HIV-1 and is currently used in salvage therapy. The genetic diversity of the env C2V3C3 region of HIV-1 strains from injecting drug users in the Greater Lisbon was studied, along with the presence of natural genetic polymorphisms. 52 plasma samples were used and the amplification by RT-nested PCR of a 565 bp-product was possible in 35 of them. The phylogenetic analysis revealed 23 sequences classified as subtype B (probably including 2 CRF14_BG), 8 A, 3 G and 1 F1. After translation, the presence of natural genetic polymorphisms was studied by comparison to a subtype B consensus. A high frequency of genetic polymorphisms was observed and significant “amino acid signatures” were found in association with non-B subtypes. A full characterization of the N-glycosylation sites was also…

Subjects/Keywords: HIV Infections; Drug Utilization; Receptors, CCR5 ; Urban Population ; Antirectroviral Therapy, Highly Active; Case Studies; Microbiologia

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sousa, C. I. C. d. (2012). Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa. (Thesis). Universidade Nova. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8170

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sousa, Carina Isabel Correia de. “Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa.” 2012. Thesis, Universidade Nova. Accessed March 07, 2021. http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8170.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sousa, Carina Isabel Correia de. “Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa.” 2012. Web. 07 Mar 2021.

Vancouver:

Sousa CICd. Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa. [Internet] [Thesis]. Universidade Nova; 2012. [cited 2021 Mar 07]. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8170.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sousa CICd. Diversidade genética e resistência natural ao Maraviroc em estirpes do vírus da imunodeficiência humana Tipo 1 (HIV-1) em circulação em utilizadores de drogas por via endovenosa na Grande Lisboa. [Thesis]. Universidade Nova; 2012. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/8170

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade Nova

27. Amaral, Sandra Margarida Caldas. Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance.

Degree: 2009, Universidade Nova

URL: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/5038

► Resumo: A decisão da terapêutica hormonal no tratamento do cancro da mama baseiase na determinação do receptor de estrogénio alfa por imunohistoquímica (IHC). Contudo, a… (more)

▼ Resumo: A decisão da terapêutica hormonal no tratamento do cancro da mama baseiase na determinação do receptor de estrogénio alfa por imunohistoquímica (IHC). Contudo, a presença deste receptor não prediz a resposta em todas as situações, em parte devido a limitações do método IHC. Investigámos se a expressão dos genes ESR1 e ESR2, bem como a metilação dos respectivos promotores, pode estar relacionada com a evolução desfavorável de uma proporção de doentes tratados com tamoxifeno assim como com a perda dos receptores de estrogénio alfa (ERα) e beta (ERß). Amostras de 211 doentes com cancro da mama diagnosticado entre 1988 e 2004, fixadas em formalina e preservadas em parafina, foram utilizadas para a determinação por IHC da presença dos receptores ERα e ERß. O mRNA total do gene ESR1 e os níveis específicos do transcrito derivado do promotor C (ESR1_C), bem como dos transcritos ESR2_ß1, ESR2_ß2/cx, and ESR2_ß5 foram avaliados por Real-time PCR. Os promotores A e C do gene ESR1 e os promotores 0K e 0N do gene ESR2 foram investigados por análise de metilação dos dinucleotidos CpG usando bisulfite-PCR para análise com enzimas de restrição, ou para methylation specific PCR. Atendendo aos resultados promissores relacionados com a metilação do promotor do gene ESR1, complementamos o estudo com um método quantitativo por matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) suportado pelo software Epityper para a medição da metilação nos promotores A e C. Fez-se a avaliação da estabilidade do mRNA nas linhas celulares de cancro da mama MCF-7 e MDA-MB-231 tratadas com actinomicina D. Baixos níveis do transcrito ESR1_C associaram-se a uma melhor sobrevivência global (p = 0.017). Níveis elevados do transcrito ESR1_C associaram-se a uma resposta inferior ao tamoxifeno (HR = 2.48; CI 95% 1.24-4.99), um efeito mais pronunciado em doentes com tumores de fenótipo ERα/PgR duplamente positivo (HR = 3.41; CI 95% 1.45-8.04). A isoforma ESR1_C mostrou ter uma semi-vida prolongada, bem como uma estrutura secundária da região 5’UTR muito mais relaxada em comparação com a isoforma ESR1_A. A análise por Western-blot mostrou que ao nível da 21 proteína, a selectividade de promotores é indistinguivel. Não se detectou qualquer correlação entre os níveis das isoformas do gene ESR2 ou entre a metilação dos promotores do gene ESR2, e a detecção da proteína ERß. A metilação do promotor C do gene ESR1, e não do promotor A, foi responsável pela perda do receptor ERα. Estes resultados sugerem que os níveis do transcrito ESR1_C sejam usados como um novo potencial marcador para o prognóstico e predição de resposta ao tratamento com tamoxifeno em doentes com cancro da mama. Abstract: The decision of endocrine breast cancer treatment relies on ERα IHC-based assessment. However, ER positivity does not predict response in all cases in part due to IHC methodological limitations. We investigated whether ESR1 and ESR2 gene expression and respective promoter methylation may be related to non-favorable outcome of a… Advisors/Committee Members: Brauch, Hiltrud, Coelho, José Luis Passos.

Subjects/Keywords: Receptors, Estrogen; Tamoxifen-therapeutic use; Breast Neoplasms-drug therapy; Breast Neoplasm-genetics; Obstetrícia e Ginecologia

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Amaral, S. M. C. (2009). Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance. (Thesis). Universidade Nova. Retrieved from http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/5038

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Amaral, Sandra Margarida Caldas. “Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance.” 2009. Thesis, Universidade Nova. Accessed March 07, 2021. http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/5038.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Amaral, Sandra Margarida Caldas. “Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance.” 2009. Web. 07 Mar 2021.

Vancouver:

Amaral SMC. Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance. [Internet] [Thesis]. Universidade Nova; 2009. [cited 2021 Mar 07]. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/5038.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Amaral SMC. Estrogen receptor dependent genetic and epigenetic factors of tamoxifen resistance. [Thesis]. Universidade Nova; 2009. Available from: http://www.rcaap.pt/detail.jsp?id=oai:run.unl.pt:10362/5038

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Riva, Clemence. Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae).

Degree: Docteur es, Physiologie et biologie des organismes - populations - interactions, 2017, Normandie

URL: http://www.theses.fr/2017NORMC420

►

L’acarien Varroa destructor est l’un des principaux responsables de l’effondrement des colonies d’abeilles domestique Apis mellifera. L’arsenal thérapeutique disponible pour lutter contre ce parasite ubiquiste… (more)

▼

L’acarien Varroa destructor est l’un des principaux responsables de l’effondrement des colonies d’abeilles domestique Apis mellifera. L’arsenal thérapeutique disponible pour lutter contre ce parasite ubiquiste apparait insuffisant à ce jour. Dans le cadre de cette thèse, la démarche de drug design, généralement utilisée en santé humaine, a été appliquée pour le développement de nouveaux médicaments vétérinaire à usage varroacide. Les travaux de cette thèse se sont focalisés sur deux cibles du système nerveux : l’acétylcholinestérase et les récepteurs à l’octopamine. Ces deux cibles ont déjà montré leur intérêt varroacide, notamment au travers des médicaments contenant du coumaphos ou de l’amitraze. Concernant l’acétylcholinestérase, un criblage fait avec le modèle 3D de l’enzyme, construit par homologie de séquences, a permis d’identifier deux composés de la chimiothèque du CERMN. Nous avons également exploré le potentiel varroacide d’acaricides de la famille des carbamates, démontrant l’intérêt du pirimicarbe comme varroacide. Concernant l’octopamine, l’étude de quatre dérivés de l’amitraze a montré l’intérêt de l’un d’entre eux. Un criblage par similarité de structure avec ce dérivé a mis en exergue une molécule issue de la chimiothèque du CERMN. Toutes les molécules pointées par ces travaux de thèse montrent de bons résultats lors de tests in vitro ou in vivo. Toutefois, afin de minimiser le risque pour l’abeille et maximiser l’efficacité anti-varroa, ces leads doivent être optimisés avant d’être ajouté à l’arsenal des médicaments varroacides.

The mite Varroa destructor is one of the main contributors to the collapse of honey bee colonies Apis mellifera. The therapeutic arsenal available against this ubiquitous parasite appears insufficient to date. In this thesis, the drug design approach, generally used in human health, was applied to the development of new varroacide veterinary drugs.The works of this thesis focused on two nervous system targets: acetylcholinesterase and octopamine receptors. These two targets have already shown their varroacide interest, especially through drugs containing coumaphos or amitraz. Regarding acetylcholinesterase, a screening made on the 3D model of the enzyme, built by sequence homology, allowed to identify two compounds from the CERMN compound library. We also explored the varroacide potential of carbamate acaricides, demonstrating the interest of pirimicarb as a varroacide. Regarding octopamine, the study of four derivatives of amitraz has shown the interest of one of them. Structural similarity screening with this derivative highlighted one hit from the CERMN compound library. All molecules pointed out by these thesis works show good results during in vitro or in vivo tests. However, to minimize the risk to honey bees and maximize their anti-varroa efficiency, these leads need to be optimized before being added to the arsenal of varroacide drugs.

Advisors/Committee Members: Sopkovà-de Oliveira Santos, Jana (thesis director), Halm-Lemeille, Marie-Pierre (thesis director).

Subjects/Keywords: Varroacide; Récepteurs à l'octopamine; Tests in vivo; Honey bee; Octopamine receptors; Drug design

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Riva, C. (2017). Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae). (Doctoral Dissertation). Normandie. Retrieved from http://www.theses.fr/2017NORMC420

Chicago Manual of Style (16^th Edition):

Riva, Clemence. “Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae).” 2017. Doctoral Dissertation, Normandie. Accessed March 07, 2021. http://www.theses.fr/2017NORMC420.

MLA Handbook (7^th Edition):

Riva, Clemence. “Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae).” 2017. Web. 07 Mar 2021.

Vancouver:

Riva C. Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae). [Internet] [Doctoral dissertation]. Normandie; 2017. [cited 2021 Mar 07]. Available from: http://www.theses.fr/2017NORMC420.

Council of Science Editors:

Riva C. Application de la démarche de drug-design pour la conception de nouveaux médicaments vétérinaires contre le parasite Varroa destructor (Acari ˸ Varroidae) : Application of the drug-design approach for the design of new veterinary drugs against the parasite Varroa destructor (Acari ˸ Varroidae). [Doctoral Dissertation]. Normandie; 2017. Available from: http://www.theses.fr/2017NORMC420

New Jersey Institute of Technology

29. Kim, Alyssa Misoo. Engineering spores to display g protein-coupled receptors for directed evolution.

Degree: MSin Pharmaceutical Engineering - (M.S.), Chemical, Biological and Pharmaceutical Engineering, 2013, New Jersey Institute of Technology

URL: https://digitalcommons.njit.edu/theses/174

► All human cells are surrounded by a plasma membrane made from a phospholipid bilayer, which is responsible for maintaining a biologically active species, while… (more)

Subjects/Keywords: Protein engineering; G protein-coupled receptors; Chemical Engineering; Pharmaceutics and Drug Design

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kim, A. M. (2013). Engineering spores to display g protein-coupled receptors for directed evolution. (Thesis). New Jersey Institute of Technology. Retrieved from https://digitalcommons.njit.edu/theses/174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kim, Alyssa Misoo. “Engineering spores to display g protein-coupled receptors for directed evolution.” 2013. Thesis, New Jersey Institute of Technology. Accessed March 07, 2021. https://digitalcommons.njit.edu/theses/174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kim, Alyssa Misoo. “Engineering spores to display g protein-coupled receptors for directed evolution.” 2013. Web. 07 Mar 2021.

Vancouver:

Kim AM. Engineering spores to display g protein-coupled receptors for directed evolution. [Internet] [Thesis]. New Jersey Institute of Technology; 2013. [cited 2021 Mar 07]. Available from: https://digitalcommons.njit.edu/theses/174.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kim AM. Engineering spores to display g protein-coupled receptors for directed evolution. [Thesis]. New Jersey Institute of Technology; 2013. Available from: https://digitalcommons.njit.edu/theses/174

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Gothenburg / Göteborgs Universitet

30. Hjorth, Stephan, 1953-. On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system.

Degree: 1983, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/11672

Subjects/Keywords: Medicin Allmänt Receptors; dopamine: drug effects

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hjorth, Stephan, 1. (1983). On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/11672

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hjorth, Stephan, 1953-. “On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system.” 1983. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed March 07, 2021. http://hdl.handle.net/2077/11672.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hjorth, Stephan, 1953-. “On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system.” 1983. Web. 07 Mar 2021.

Vancouver:

Hjorth, Stephan 1. On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 1983. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/2077/11672.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hjorth, Stephan 1. On the mode of action of 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, and its enantiomers : with particular reference to dopaminergic mechanisms in the central nervous system. [Thesis]. University of Gothenburg / Göteborgs Universitet; 1983. Available from: http://hdl.handle.net/2077/11672

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

		in
And / Or
		in
And / Or
		in
And / Or
		in

Open Access Theses and Dissertations