subject:(tyrosyl DNA phosphodiesterase 1)

University of Edinburgh

1. Carloni, Roberta. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/18015

► In order to evaluate the suitability of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) as a potential drug target for an anti-parasite therapy, we… (more)

Subjects/Keywords: 572.8; DNA repair; topoisomerase; TDP1; tyrosyl-DNA phosphodiesterase 1; T. brucei

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APA (6^th Edition):

Carloni, R. (2014). Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/18015

Chicago Manual of Style (16^th Edition):

Carloni, Roberta. “Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed April 16, 2021. http://hdl.handle.net/1842/18015.

MLA Handbook (7^th Edition):

Carloni, Roberta. “Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.” 2014. Web. 16 Apr 2021.

Vancouver:

Carloni R. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1842/18015.

Council of Science Editors:

Carloni R. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/18015

University of Illinois – Chicago

2. Li, Jing. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).

Degree: 2017, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/22078

► The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination… (more)

▼ The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. Major DSB repair pathways in mammalian cells include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggest that NHEJ includes mechanisms to minimize error. In yeast, mutations of tyrosyl-DNA phosphodiesterase 1 (TDP1) reduced NHEJ fidelity. We are investigating the role of TDP1 in NHEJ in human cells. Using affinity capture chromatography, we found human TDP1 physically interacted with the required NHEJ protein -XLF. This interaction also stimulated DNA binding for both TDP1 and XLF, and formation of TDP1:XLF:DNA complexes. TDP1 can remove adducts from DNA 3’ ends, and TDP1:XLF interactions stimulated this activity on double-stranded, but not on single-stranded DNA. To investigate role of TDP1 in NHEJ in human cells, we used CRISPR/Cas9-mediated genome editing to generate TDP1-knockout HEK 293 cells, which showed an expected increase sensitivity to Topoisomerase 1 poisoning and ionizing radiation. Using a chromosomally- integrated end-joining reporter substrate, we observed an average 4-fold reduction in repair of I-SceI-induced DSBs in TDP1-KO cells as compared to wild type cells. These data indicate that, in human cells, TDP1 contributes to repair of DSBs that lack 3’ end damage. NextGen sequencing of end-joining junctions generated in this reporter system showed that TDP1 deficiency resulted in increased use of microhomology in joining. Within the N-terminal domain of TDP1, phosphorylation at serine 81 (S81) has been reported to regulate interaction with DNA repair factors, including DNA ligase III, XRCC4 and PARP1. We observed that the TDP1-S81 phosphomimetic, TDP1-S81E, had 10-fold reduced XLF binding, and ectopic expression of TDP1-S81E in TDP1-knockout cells failed to restore NHEJ activity. These data suggest that phosphorylation of TDP1-S81 regulates TDP1 participation in NHEJ, and may also direct TDP1 towards DNA ligase III-related pathways. Our observations support the hypothesis that TDP1 participates in mammalian NHEJ, and contribute important details to our understanding of DNA repair. Advisors/Committee Members: Hanakahi, Les (advisor), Nitiss, John (committee member), Mankin, Alexander (committee member), Burdette, Joanna (committee member), Thomas, Douglas (committee member), Hanakahi, Les (chair).

Subjects/Keywords: tyrosyl-DNA phosphodiesterase 1 (TDP1); non-homologous end joining (NHEJ); DNA double-strand breaks (DSB)

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APA (6^th Edition):

Li, J. (2017). Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/22078

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):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Thesis, University of Illinois – Chicago. Accessed April 16, 2021. http://hdl.handle.net/10027/22078.

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

MLA Handbook (7^th Edition):

Li, Jing. “Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ).” 2017. Web. 16 Apr 2021.

Vancouver:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Internet] [Thesis]. University of Illinois – Chicago; 2017. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/10027/22078.

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

Council of Science Editors:

Li J. Investigating Role of Tyrosyl-DNA Phosphodiesterase 1 (TDP1) In Non-Homologous End Joining (NHEJ). [Thesis]. University of Illinois – Chicago; 2017. Available from: http://hdl.handle.net/10027/22078

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

University of Kansas

3. Jun, Jung Ho. Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen.

Degree: PhD, Chemistry, 2013, University of Kansas

URL: http://hdl.handle.net/1808/19567

► Sulfur containing compounds have become increasingly important in the development of biological agents for pharmaceutical and industrial use. Cyclic sulfamides, in particular, have been found… (more)

▼ Sulfur containing compounds have become increasingly important in the development of biological agents for pharmaceutical and industrial use. Cyclic sulfamides, in particular, have been found to be useful as cancer, HIV protease inhibitors and other therapeutic treatments. As the need for new and improved inhibitors is warranted by the serious cancer disease, the search for new synthetic pathways to access novel sulfamides is ongoing. To this end, the work discussed herein focuses on the synthesis of newly developed sulfamides utilizing the reductive amination and Mitsunobu reaction to generate novel chiral amino ester containing sulfamide compounds. These compounds are being screened for their biological activities as Tyrosyl-DNA phosphodiesterase 1 (Tdp 1) inhibitors and anti-cancer drugs. Initially, reductive amination, CSI coupling, and Mitsunobu reaction were employed to generate piperidinyl sulfamides, and these compounds were screened for Tdp1 inhibition. These compounds were submitted to Dr. Pomier's group at NIH to carry out the gel study to select active compounds. We also checked the binding effect through the protein docking study. In addition, these sulfamide compounds were screened from NCI 60-cancer cell lines to check the bioactivity and in vitro cytotoxicity evaluation. To understand anti-cancer activity of cyclic sulfamides, symmetric and unsymmetric seven-membered sulfamides compounds were tested in 60 cancer cell line from the National Cancer Institute. These compounds were made when I studied for the Master degree at the University of Kansas. RCM was employed to generate symmetric seven-membered cyclic sulfamides similar in structure to known active HIV protease inhibitor DMP 323. Functionalization of these compounds employing "robust S-linchpins" in conjunction with RCM yields an array of new S-heterocycles. Further work in sulfamides employed a combination of RCM with different coupling routes to generate unsymmetric seven-membered cyclic sulfamides with varied substitution in their P1/P1' and P2/P2' periphery in attempts to broaden the scope of this chemistry and to generate new biologically active compounds. Advisors/Committee Members: Hanson, Paul R (advisor), Malhotra, Sanjay V (advisor), Givens, Richard S (cmtemember), Tunge, Jon (cmtemember), Prisinzano, Thomas E (cmtemember), Mure, Minae (cmtemember).

Subjects/Keywords: Chemistry; cancer; cyclic sulfamide; NCI 60 cancer cell line; Oncology; Sulfamide; Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors

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APA (6^th Edition):

Jun, J. H. (2013). Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/19567

Chicago Manual of Style (16^th Edition):

Jun, Jung Ho. “Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen.” 2013. Doctoral Dissertation, University of Kansas. Accessed April 16, 2021. http://hdl.handle.net/1808/19567.

MLA Handbook (7^th Edition):

Jun, Jung Ho. “Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen.” 2013. Web. 16 Apr 2021.

Vancouver:

Jun JH. Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen. [Internet] [Doctoral dissertation]. University of Kansas; 2013. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1808/19567.

Council of Science Editors:

Jun JH. Newly Developed Piperidinyl Sulfamides as Tyrosyl-DNA Phosphodiesterase 1 (Tdp 1) Inhibitors, and Study of Anticancer Activity of Piperidinyl Sulfamides Derivatives and Seven-Membered Cyclic Sulfamide Analogs Using the National Cancer Institute 60 Human Cancer Cell Line (NCI 60) Screen. [Doctoral Dissertation]. University of Kansas; 2013. Available from: http://hdl.handle.net/1808/19567

Florida International University

4. Wang, Wenjie. Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs.

Degree: PhD, Chemistry, 2019, Florida International University

URL: https://digitalcommons.fiu.edu/etd/4254 ; FIDC007779

► Glioblastoma (GBM) patients have an estimated survival of ~15 months, with the standard of care (surgery, radiation, and chemotherapy) that has only modestly enhanced… (more)

▼ Glioblastoma (GBM) patients have an estimated survival of ~15 months, with the standard of care (surgery, radiation, and chemotherapy) that has only modestly enhanced patient survival. Identifying biomarkers representing vulnerabilities in GBM biology may allow for the selection of effective and safe chemotherapy options. Irinotecan (IRT), a genotoxic compound currently in clinical trials for GBM, targets topoisomerase I (TOP1) by forming an irreversible ternary DNA-TOP1 cleavage complex (TOP1cc) and leads to apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that rescues TOP1cc and reduces the effectiveness of IRT. In the current study, we evaluate the value of the TDP1/TOP1 activity ratio as a prospective biomarker for the personalized use of IRT on GBM patients. After analysis of susceptibility of nine GBM cell lines to IRT treatment along with TDP1 and TOP1 expression and activity levels in these cell lines, we found that the TDP1/TOP1 activity ratio had the strongest correlation (R=0.972, P=1.2×10^-5) with IRT IC₅₀values for a decrease of cell viability following IRT treatment. Increasing the TDP1/TOP1 activity ratio by ectopic expression of wild-type TDP1 increased in IRT IC₅₀, while expression of the TDP1 catalytic-null mutant did not alter the susceptibility to IRT. Further, after analyzing GBM patient tumors, TDP/TOP1 activity ratio was found to correlate (R=-0.707, P=0.03) with patient survival significantly. Correlations were also observed between patient age and survival this set of GBM patients (R=-0.929, P=0.023) as well as GBM patients in the TCGA database (R=-0.353, P=7.7×10^-17). From our results, we suggested that the TDP1/TOP1 activity ratio may be a new predictive indicator for GBM vulnerability to IRT, which may allow for the selection of individual patients for IRT treatment based on risk-benefit. As a predictor, the lower TDP1/TOP1 activity ratio would correspond to higher IRT cytotoxicity. In addition, TDP1/TOP1 activity ratio might be a potential prognostic indicator for GBM patient survival. The lower TDP1/TOP1 ratio would correspond to patients with longer survival probability. Finally, inhibitors of TDP1 may be useful for novel combination therapy with IRT to improve GBM patient responsiveness to genotoxic chemotherapies. Advisors/Committee Members: Yuk-Ching Tse-Dinh, Alexander Mebel, Jeremy Chambers, Watson Lees, Yuan Liu.

Subjects/Keywords: glioblastoma; topoisomerase; tyrosyl-DNA phosphodiesterase; Biochemistry; Biological Factors; Enzymes and Coenzymes; Nervous System Diseases

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

APA (6^th Edition):

Wang, W. (2019). Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/4254 ; FIDC007779

Chicago Manual of Style (16^th Edition):

Wang, Wenjie. “Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs.” 2019. Doctoral Dissertation, Florida International University. Accessed April 16, 2021. https://digitalcommons.fiu.edu/etd/4254 ; FIDC007779.

MLA Handbook (7^th Edition):

Wang, Wenjie. “Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs.” 2019. Web. 16 Apr 2021.

Vancouver:

Wang W. Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs. [Internet] [Doctoral dissertation]. Florida International University; 2019. [cited 2021 Apr 16]. Available from: https://digitalcommons.fiu.edu/etd/4254 ; FIDC007779.

Council of Science Editors:

Wang W. Topoisomerase and Tyrosyl-DNA-phosphodiesterase Ratio as an Indicator for the Response of Glioblastoma Cancer to Topoisomerase Targeting Anticancer Drugs. [Doctoral Dissertation]. Florida International University; 2019. Available from: https://digitalcommons.fiu.edu/etd/4254 ; FIDC007779

University of Edinburgh

5. Roberts, Fiona. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.

Degree: PhD, 2020, University of Edinburgh

URL: http://hdl.handle.net/1842/37003

► The skeleton is a mineralised tissue, which facilitates classical functions of locomotion, organ protection and mineral homeostasis. However, the bone has more recently been identified… (more)

▼ The skeleton is a mineralised tissue, which facilitates classical functions of locomotion, organ protection and mineral homeostasis. However, the bone has more recently been identified as an endocrine organ with the ability to regulate systemic glucose and thus energy metabolism. The acknowledgement of this previously unanticipated role of the skeleton emerged following the identification of a novel role of osteocalcin. This osteoblast-secreted hormone promotes peripheral insulin sensitivity and secretion by the pancreas. Within the bone and endocrine field, attention is now being paid to delineating further roles of proteins known to regulate mineralisation. These proteins either promote or inhibit mineralisation through various enzymatic pathways. Ectonucleotide pyrophosphatase phosphodiesterase-1 (NPP1 in mice, ENPP1 in humans) is recognised as a mineralisation regulator. By the hydrolysis of ATP, this enzyme generates extracellular pyrophosphate (PPi) which is a potent inhibitor of mineralisation (e.g. for bone and soft tissue such as the vasculature). However, NPP1 is also recognised as a pathogenic factor for insulin resistance, whereby it binds to the insulin receptor (IR) and abrogates downstream glucose mediation. This may lead to the development of insulin resistance which is a prerequisite for type 2 diabetes mellitus. Previous work has demonstrated that the global knockout of NPP1 in mice (Enpp1-/-) leads to pathological mineralisation, systemically reduced serum PPi and protection against insulin resistance and obesity following chronic high-fat diet feeding. However, the cell-specific contributions of NPP1 to the bone and metabolic phenotype remains unknown. The data presented in this thesis has expanded on this previous work by investigating the bone and metabolic phenotype of an osteoblast-specific NPP1 knockout mouse model (Enpp1flox/flox;Ocn-cre) compared to controls (Enpp1flox/flox). Previous work has shown that global Enpp1 knockout mice present with severe joint hypermineralisation, spinal ankylosis and soft tissue mineralisation (e.g. the tunica media of the aorta). These mice also present with a paradoxical hypomineralisation of the long bone diaphysis. In contrast, the work presented in this thesis includes a detailed analysis of the bone phenotype which revealed a significantly increased bone mass and bone mineral density in the Enpp1flox/flox;Ocn-cre. This finding was supported by in vitro analysis of primary osteoblasts isolated from the Enpp1flox/flox;Ocn-cre mice and grown under mineralising conditions. This in vitro work demonstrated that Enpp1flox/flox;Ocncre isolated osteoblasts mineralise more quickly, and to a greater extent, compared to their controls. This work also revealed that systemic levels of PPi remain unchanged in the Enpp1flox/flox;Ocn-cre mice; indeed these mice have an absence of pathological soft tissue mineralisation likely as a product of this. The metabolic phenotype of Enpp1flox/flox;Ocn-cre mice was assessed following both control and high-fat diet feeding. In vivo…

Subjects/Keywords: ectonucleotide pyrophosphatase/phosphodiesterase-1; NPP1; osteoblasts; insulin resistance; mouse model

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

APA (6^th Edition):

Roberts, F. (2020). Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/37003

Chicago Manual of Style (16^th Edition):

Roberts, Fiona. “Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed April 16, 2021. http://hdl.handle.net/1842/37003.

MLA Handbook (7^th Edition):

Roberts, Fiona. “Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.” 2020. Web. 16 Apr 2021.

Vancouver:

Roberts F. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1842/37003.

Council of Science Editors:

Roberts F. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: http://hdl.handle.net/1842/37003

University of Edinburgh

6. Roberts, Fiona. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.

Degree: PhD, 2020, University of Edinburgh

URL: https://doi.org/10.7488/era/304 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.806198

► The skeleton is a mineralised tissue, which facilitates classical functions of locomotion, organ protection and mineral homeostasis. However, the bone has more recently been identified… (more)

▼ The skeleton is a mineralised tissue, which facilitates classical functions of locomotion, organ protection and mineral homeostasis. However, the bone has more recently been identified as an endocrine organ with the ability to regulate systemic glucose and thus energy metabolism. The acknowledgement of this previously unanticipated role of the skeleton emerged following the identification of a novel role of osteocalcin. This osteoblast-secreted hormone promotes peripheral insulin sensitivity and secretion by the pancreas. Within the bone and endocrine field, attention is now being paid to delineating further roles of proteins known to regulate mineralisation. These proteins either promote or inhibit mineralisation through various enzymatic pathways. Ectonucleotide pyrophosphatase phosphodiesterase-1 (NPP1 in mice, ENPP1 in humans) is recognised as a mineralisation regulator. By the hydrolysis of ATP, this enzyme generates extracellular pyrophosphate (PPi) which is a potent inhibitor of mineralisation (e.g. for bone and soft tissue such as the vasculature). However, NPP1 is also recognised as a pathogenic factor for insulin resistance, whereby it binds to the insulin receptor (IR) and abrogates downstream glucose mediation. This may lead to the development of insulin resistance which is a prerequisite for type 2 diabetes mellitus. Previous work has demonstrated that the global knockout of NPP1 in mice (Enpp1-/-) leads to pathological mineralisation, systemically reduced serum PPi and protection against insulin resistance and obesity following chronic high-fat diet feeding. However, the cell-specific contributions of NPP1 to the bone and metabolic phenotype remains unknown. The data presented in this thesis has expanded on this previous work by investigating the bone and metabolic phenotype of an osteoblast-specific NPP1 knockout mouse model (Enpp1flox/flox;Ocn-cre) compared to controls (Enpp1flox/flox). Previous work has shown that global Enpp1 knockout mice present with severe joint hypermineralisation, spinal ankylosis and soft tissue mineralisation (e.g. the tunica media of the aorta). These mice also present with a paradoxical hypomineralisation of the long bone diaphysis. In contrast, the work presented in this thesis includes a detailed analysis of the bone phenotype which revealed a significantly increased bone mass and bone mineral density in the Enpp1flox/flox;Ocn-cre. This finding was supported by in vitro analysis of primary osteoblasts isolated from the Enpp1flox/flox;Ocn-cre mice and grown under mineralising conditions. This in vitro work demonstrated that Enpp1flox/flox;Ocncre isolated osteoblasts mineralise more quickly, and to a greater extent, compared to their controls. This work also revealed that systemic levels of PPi remain unchanged in the Enpp1flox/flox;Ocn-cre mice; indeed these mice have an absence of pathological soft tissue mineralisation likely as a product of this. The metabolic phenotype of Enpp1flox/flox;Ocn-cre mice was assessed following both control and high-fat diet feeding. In vivo…

Subjects/Keywords: 612.7; ectonucleotide pyrophosphatase/phosphodiesterase-1; NPP1; osteoblasts; insulin resistance; mouse model

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

APA (6^th Edition):

Roberts, F. (2020). Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. (Doctoral Dissertation). University of Edinburgh. Retrieved from https://doi.org/10.7488/era/304 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.806198

Chicago Manual of Style (16^th Edition):

Roberts, Fiona. “Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.” 2020. Doctoral Dissertation, University of Edinburgh. Accessed April 16, 2021. https://doi.org/10.7488/era/304 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.806198.

MLA Handbook (7^th Edition):

Roberts, Fiona. “Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism.” 2020. Web. 16 Apr 2021.

Vancouver:

Roberts F. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. [Internet] [Doctoral dissertation]. University of Edinburgh; 2020. [cited 2021 Apr 16]. Available from: https://doi.org/10.7488/era/304 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.806198.

Council of Science Editors:

Roberts F. Investigating the impact of osteoblast-specific NPP1 ablation on bone and energy metabolism. [Doctoral Dissertation]. University of Edinburgh; 2020. Available from: https://doi.org/10.7488/era/304 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.806198

University of British Columbia

7. Lee, Jack Foo. The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue.

Degree: MS- MSc, Pharmacology, 1967, University of British Columbia

URL: http://hdl.handle.net/2429/36418

► During the past 50 years, a number of nucleophosphodiesterases have been studied. Of recent interest, is a brain phosphodiesterase which converts ribonucleoside 2',3'-cyclic phosphates to… (more)

▼ During the past 50 years, a number of nucleophosphodiesterases have been studied. Of recent interest, is a brain phosphodiesterase which converts ribonucleoside 2',3'-cyclic phosphates to the corresponding ribonucleoside 2'-phosphates. The physiological role of this enzyme is entirely unknown. The present studies were designed to learn something of its intracellular distribution, properties and mechanism of action. The assay of the enzyme was based on the hydrolysis of adenosine 2', 3'-cyclic phosphate by the diesterase followed by the hydrolysis of the reaction product with alkaline phosphatase and subsequent analysis for inorganic phosphate by a modified method of Fiske and SubbaRow. Rabbit brain homogenate was fractionated into nuclear, mitochondrial, microsomal and 100,000 x g supernatant fluid fractions by differential centrifugation. 2',3'-Cyclic phosphodiesterase activity was found in all the fractions with the greatest activity in the mitochondrial fraction. Since the mitochondrial fraction was a heterogenous mixture as revealed by electron microscopy, its components were separated by sucrose density gradient centrifugation by established methods. Five subtractions were obtained (A, B, C, D, E). The lightest subfraction (A) contained most of the diesterase activity and electron microscopy revealed that this subfraction consisted of fragments of myelin of various sizes. The microsomal and nuclear fractions were also subjected to sucrose density gradient centrifugation. Again, the least dense, myelin-containing sub-fraction, contained most of the diesterase activity. It was also found that rabbit brain white matter contained greater diesterase activity than grey matter. The data provide strong evidence that the diesterase is associated with myelin. It was found that acetone extraction of the myelin fraction from a homogenate of white matter of beef brain resulted in a doubling of diesterase activity with a five-fold purification. Efforts directed toward solubilization of the enzyme were unsuccessful. Some properties of the enzyme were also determined. The diesterase opened the cyclic diester bond of cyclic-ended oligonucleotides, at least as large as (A₈) and did so, without cleavage of internucleotide bonds. It was inactivated by the sulfhydryl reagent, para-hydroxymercuribenzoate, and was unaffected by the presence of a wide variety of purine and pyrimidine compounds or derivatives and various nucleoside mono-, di- and triphosphates. The Km of the diesterase was determined to be 1.9 x 10⁻³ M.

Subjects/Keywords: Phosphodiesterase

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

APA (6^th Edition):

Lee, J. F. (1967). The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue. (Masters Thesis). University of British Columbia. Retrieved from http://hdl.handle.net/2429/36418

Chicago Manual of Style (16^th Edition):

Lee, Jack Foo. “The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue.” 1967. Masters Thesis, University of British Columbia. Accessed April 16, 2021. http://hdl.handle.net/2429/36418.

MLA Handbook (7^th Edition):

Lee, Jack Foo. “The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue.” 1967. Web. 16 Apr 2021.

Vancouver:

Lee JF. The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue. [Internet] [Masters thesis]. University of British Columbia; 1967. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2429/36418.

Council of Science Editors:

Lee JF. The enzymatic hydrolysis of ribonucleoside 2', 3'-cyclic phospates by a diesterase in nerve tissue. [Masters Thesis]. University of British Columbia; 1967. Available from: http://hdl.handle.net/2429/36418

University of Adelaide

8. Gargett, Tessa. Optimising DNA vaccine technology to prevent HIV-1 infection.

Degree: 2013, University of Adelaide

URL: http://hdl.handle.net/2440/92659

► The failure of traditional protein-based vaccines to prevent HIV infection highlights the need for novel vaccine strategies. An effective HIV-1 vaccine will need to induce… (more)

▼ The failure of traditional protein-based vaccines to prevent HIV infection highlights the need for novel vaccine strategies. An effective HIV-1 vaccine will need to induce cell-mediated and humoral immune responses at both systemic and mucosal sites. DNA based vaccines are appealing candidates for novel vaccines because they are inexpensive, stable and simple to manufacture. They also mimic a viral infection, by using cellular machinery to produce vaccine antigens in the same way that viruses hijack the host cell to produce viral proteins and nucleic acids, but are not infectious themselves. DNA vaccines effectively induce both humoral and cell mediated immune responses to viral antigens, however despite being licensed for veterinary use they have so far been insufficiently immunogenic in human trials. To realise the potential of DNA vaccines, the technology must first be optimised to improve both delivery and immunogenicity. In this thesis I have proposed two novel approaches to optimise DNA vaccines. Firstly, to improve delivery, I have proposed the use of influenza virosomes as a delivery vehicle for the intranasal administration of DNA vaccines. Intranasal vaccination is known to induce pan-mucosal immune responses at distant sites such as the genital mucosa. This concept is particularly important for HIV vaccines, as it is believed that an early immune response at the genital mucosa offers the best chance to control HIV infection before it becomes systemic. In this thesis I have used live imaging of the reporter molecule, luciferase, to confirm efficient intranasal delivery of DNA vaccines by influenza virosomes, and this is the first time that visualisation of this process has been reported, I have also demonstrated that intranasal delivery of virosome-encapsulated DNA can enhance the mucosal immune response. Secondly, to improve immunogenicity, I have proposed the use of suicide genes to induce cell necrosis and provide an adjuvant effect for DNA vaccines. Necrotic, antigen-positive cells release a range of intracellular factors that signal via receptors on dendritic cells, including Toll-like receptors and ClecgA, and lead to dendritic cell activation and enhanced cross-presentation of antigen. In this thesis I have tested the novel application of the suicide genes NSP4, perforin [PRF) and DTa, which induce cell death by different mechanisms, I have provided evidence that suicide gene-induced necrosis in DNA vaccine-targeted cells provides an adjuvant effect. In this thesis I report that a DNA vaccine that induces cytolytic, rather than apoptotic, cell death enhances CD11c+ CD8α+ dendritic cell activation, broad and multifunctional CD8 T cell responses and increases protection in mice from challenge with a chimeric virus, EcoHIV. This enhancement was also dependent on the timing of cell death after antigen expression. Thus, cytolytic gene-induced necrosis resulting from co-expression of perforin and an immunogenic protein can significantly improve the immunogenicity of DNA vaccines. The work in this thesis… Advisors/Committee Members: Gowans, Eric James (advisor), Grubor-Bauk, Branka (advisor), Miller, Darren Scott (advisor), Burrell, Christopher John (advisor), School of Medicine (school).

Subjects/Keywords: DNA vaccines; necrosis; HIV-1; T cells

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

APA (6^th Edition):

Gargett, T. (2013). Optimising DNA vaccine technology to prevent HIV-1 infection. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/92659

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):

Gargett, Tessa. “Optimising DNA vaccine technology to prevent HIV-1 infection.” 2013. Thesis, University of Adelaide. Accessed April 16, 2021. http://hdl.handle.net/2440/92659.

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

MLA Handbook (7^th Edition):

Gargett, Tessa. “Optimising DNA vaccine technology to prevent HIV-1 infection.” 2013. Web. 16 Apr 2021.

Vancouver:

Gargett T. Optimising DNA vaccine technology to prevent HIV-1 infection. [Internet] [Thesis]. University of Adelaide; 2013. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2440/92659.

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

Council of Science Editors:

Gargett T. Optimising DNA vaccine technology to prevent HIV-1 infection. [Thesis]. University of Adelaide; 2013. Available from: http://hdl.handle.net/2440/92659

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

King Abdullah University of Science and Technology

9. Almulhim, Fatimah F. Structural and Dynamic Profiles of the WT hFEN1 in solution.

Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2020, King Abdullah University of Science and Technology

URL: http://hdl.handle.net/10754/664008

► Genomic DNA is under constant assault by environmental factors that introduce a variety of DNA lesions. Cells evolved several DNA repair and recombination mechanisms to… (more)

▼ Genomic DNA is under constant assault by environmental factors that introduce a variety of DNA lesions. Cells evolved several DNA repair and recombination mechanisms to remove these damages and ensure the integrity of the DNA material. A variety of specific proteins, called nucleases, processes toxic DNA structures that deviate from the heritable duplex DNA as common pathway intermediates. DNA-induced protein ordering is a common feature in all DNA repair nucleases. Still, the conformational requirement of the DNA and the protein and how they control the catalytic selectivity of the nuclease remain largely unknown. This study focus on the bases of catalytic activity of a protein belongs to the 5’ nuclease super-family called the human Flap endonuclease 1 (FEN1); it removes excess 5’ flaps that are generated during DNA replication. hFEN1 mutations and over-expression had been linked to a variety of cancers. This thesis aims to study the structural and dynamic properties of free hFEN1 and the catalytic activity of DNA-bound hFEN1 in solution utilizing the modern high-resolution multidimensional Nuclear Magnetic Resonance (NMR) spectroscopy. It was possible to depict the secondary structure and backbone conformation in solution of wild type (WT) hFEN1 by the usage of the improved list of assigned resonances, derived from the NMR 2D and 3D ¹⁵N-detected experiments and compared to the assignment with the previously published resonance assignment (BMRB id: 27160). I was successfully assigned the new spectrum and enhanced it by assigning seven more residues. Moreover, we tested the interaction of 1:10 ratio of hFEN1-Ca2+ with DNA by the ¹³C-detected 2D CACO experiment. The results indicate hFEN1:DNA interaction. Furthermore, parts of hFEN1 get more ordered/structured once DNA appears, thus we recorded the protein flexibly by 2D ¹H-¹⁵N TROSY-HSQC using the relaxation rate parameters: longitudinal R1, transverse R2 complemented with ¹⁵N-{¹H} NOEs (heteronuclear Overhauser enhancement). It was found that the overall molecular architecture is rigid, and the highest flexibility lies in the α2-α3 loop and arch (α4-α5) regions. Further analysis is needed to understand more profoundly the activity of hFEN1 in an atomic level by inducing mutations and testing the protein in various environmental conditions. Advisors/Committee Members: Jaremko, Mariusz (advisor), Falqui, Andrea (committee member), Saikaly, Pascal (committee member).

Subjects/Keywords: Flap endonuclease 1; DNA repair; NMR spectroscopy

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

APA (6^th Edition):

Almulhim, F. F. (2020). Structural and Dynamic Profiles of the WT hFEN1 in solution. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/664008

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):

Almulhim, Fatimah F. “Structural and Dynamic Profiles of the WT hFEN1 in solution.” 2020. Thesis, King Abdullah University of Science and Technology. Accessed April 16, 2021. http://hdl.handle.net/10754/664008.

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

MLA Handbook (7^th Edition):

Almulhim, Fatimah F. “Structural and Dynamic Profiles of the WT hFEN1 in solution.” 2020. Web. 16 Apr 2021.

Vancouver:

Almulhim FF. Structural and Dynamic Profiles of the WT hFEN1 in solution. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2020. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/10754/664008.

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

Council of Science Editors:

Almulhim FF. Structural and Dynamic Profiles of the WT hFEN1 in solution. [Thesis]. King Abdullah University of Science and Technology; 2020. Available from: http://hdl.handle.net/10754/664008

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

10. 조, 수진. A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway.

Degree: 2014, Ajou University

URL: http://repository.ajou.ac.kr/handle/201003/10857 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016596

►

As a member of imitation switch (ISWI) family in ATP-dependent chromatin remodeling factors, RSF complex consists of SNF2h ATPase and Rsf-1. Although it has been… (more)

▼

As a member of imitation switch (ISWI) family in ATP-dependent chromatin remodeling factors, RSF complex consists of SNF2h ATPase and Rsf-1. Although it has been reported that SNF2h ATPase is recruited to DNA damage sites (DSBs) in poly(ADP-ribosyl) polymerase 1 (PARP1)-dependent manner in DNA damage response (DDR), the function of Rsf-1 is still elusive. Here we show that Rsf-1 is recruited to DSBs confirmed by various cellular analyses (immunofluorescent microscope, micro-irradiation and stably integrated reporter system at a single DNA double-strand break). Rsf-1 rapidly accumulated at the DSB sites. Signal of γ H2AX is gradually reduced at 10 minutes after micro-irradiation whereas signals of Rsf-1 and SNF2h are still retained over 30 minutes after DNA damage. Moreover, depletion of Rsf-1 attenuates the recruitment of SNF2h and γ-H2AX. In addition, Rsf-1 accumulation at DNA damage sites requires PARP1 activity through interacting with PHD domain. Finally, we demonstrate that depletion of Rsf-1 diminishes DNA damage checkpoint signals and repair. Thus, these results reveal a new function of chromatin remodeler Rsf-1 in coordinating DNA signaling and repair.

RSF 복합체는 뉴클레오솜 이동에 관여하는 크로마틴 리모델링 인자로서 ATPase 효소 기능을 가지고 있는 SNF2h 와 Rsf-1 으로 구성되어 있다. 크로마틴 리모델링 인자들은 DNA 상에서 뉴클레오솜을 이동시키거나 뉴클레오솜을 구성하는 히스톤을 교체함으로써 DNA 복제과정이나 RNA 합성과정에 영향을 미친다는 것이 알려져 있다. 최근에 크로마틴 리모델링 인자들이 DNA 손상 시 신호 체계나 손상 복구에 관여한다는 것이 보고되기 시작하고 있다. 본 연구에서는 Rsf-1 이 DNA 손상 신호에 관여하는 지 그리고 그 작용기전에 대해 연구하고자 하였다. Rsf-1 이 DNA 손상에 관여하는지를 알아보기 위한 방법으로 우선 DNA 손상부위로 이동하는 지를 조사하였다. Laser microirradiation 방법을 사용하여 DNA 에 손상을 준 부위에 Rsf-1 이 이동하여 축적되는 것을 관찰하였다. 또한, FokI system 을 이용하여 살아있는 세포의 염색체 특정부위에 이중나선절단을 유도하였을 때에도 Rsf-1 이 DNA 손상부위에 축적되었다. Rsf-1 이 DNA 손상부위에 축적되는 것은 결합체인 SNF2h 비의존적으로 일어나며, Rsf-1 의 PHD (plant homeodomain)도메인이 중요하다는 것을 확인하였다. 또한 DNA 손상신호의 초기 마커인 γ-H2AX 보다 빨리 DNA 손상부위로 이동하고, Rsf-1 의 발현이 저하된 경우에는 γ-H2AX 의 축적이 저하되는 것으로 보아 DNA 손상시 초기에 작용할 것으로 예상된다. 흥미롭게도 Rsf-1 이 빠른 시기에 축적이 되는 것은 PARP1 억제제를 통하여 PARP1 활성에 의존하여 이루어진다는 것을 관찰하였다. 따라서 본 연구는 Rsf-1 이 DNA 손상 신호 체계에 관여하며 PARP1 활성에 의해 DNA 손상 부위로 모이게 되고 DNA 손상 신호를 조절한다는 것을 밝히고 있다.

국문요약 ⅰ 차례 ⅲ 그림차례 ⅳ Ⅰ. 서론 1 Ⅱ. 재료 및 방법(혹은 연구대상 및 방법) 5 A. Cell culture, reagent and treatment 5 B. Plasmids and RNA interference 5 C. Laser micro-irradiation 6 D. Immunofluorescence microscopy 6 E. Antibodies 7 F. FokI assay 7 G. Survival assay 7 Ⅲ. 결과 9 A. Rsf-1 is accumulated to the regions of DNA damage and remained 9 B. Rsf-1 is recruited to the DNA damage sites 10 C. Rsf-1 contributes to SNF2h recruitment to DNA damage sites 11 D. Assembly of γ-H2AX at the DSB-flanking chromatin is regulated by Rsf-1 12 E. Rsf-1 accumulation at the DNA damage sites requires PARP1 activity 12 F. PHD domain of Rsf-1 is required for the DNA damage response 13 G. Depletion of Rsf-1 diminishes cell survival and DNA damage checkpoint signals 14 Ⅳ. 고찰 26 Ⅴ. 결론 31 참고문헌 32 ABSTRACT 38

Master

Advisors/Committee Members: 대학원 의생명과학과, 201125007, 조, 수진.

Subjects/Keywords: DNA damage; chromatin remodeling factor; Rsf-1; PARP1; DNA damage checkpoint

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

APA (6^th Edition):

조, �. (2014). A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway. (Thesis). Ajou University. Retrieved from http://repository.ajou.ac.kr/handle/201003/10857 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016596

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):

조, 수진. “A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway.” 2014. Thesis, Ajou University. Accessed April 16, 2021. http://repository.ajou.ac.kr/handle/201003/10857 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016596.

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

MLA Handbook (7^th Edition):

조, 수진. “A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway.” 2014. Web. 16 Apr 2021.

Vancouver:

조 �. A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway. [Internet] [Thesis]. Ajou University; 2014. [cited 2021 Apr 16]. Available from: http://repository.ajou.ac.kr/handle/201003/10857 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016596.

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

Council of Science Editors:

조 �. A functional role of chromatin remodeling factor, Rsf-1 in the DNA damage signaling pathway. [Thesis]. Ajou University; 2014. Available from: http://repository.ajou.ac.kr/handle/201003/10857 ; http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000016596

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

University of Gothenburg / Göteborgs Universitet

11. Tang, Ka-Wei. Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription.

Degree: 2015, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/40883

► Herpes simplex virus 1 (HSV-1) is one of nine different herpesvirus infecting man. They are all capable of establishing a life-long latent state following the… (more)

▼ Herpes simplex virus 1 (HSV-1) is one of nine different herpesvirus infecting man. They are all capable of establishing a life-long latent state following the primary infection. HSV-1 as well as other herpesviruses may reactivate from the latent state and give rise to a productive infection with clinical symptoms or asymptomatic shedding. HSV-1 infections are primarily treated by targeting the viral DNA replication carried out by a molecular machinery, a replisome, encoded by the virus. Here we examine the mechanism of initiation of viral DNA replication and also how viral DNA replication interacts with DNA recombination and gene expression. In our first study we examined the initiation-step of HSV-1 replication. The origin binding protein (OBP) initiates replication by binding to the origin of replication (oriS and/or oriL). We showed, using phylogenetics and biochemical experiments, that there was a step-wise evolutionary development of herpesvirus DNA replication initiation. The initial divergence was seen in herpesviruses acquiring an amino-acid motif RVKNL in OBP which binds the sequence TTCGCAC in the oriS. The next step was the development of an ICP8 binding motif at the C-terminus of OBP and finally the arrangement of the binding-sites for OBP in the oriS-sequence and the ability to form a stable hairpin. We presented molecular in vitro data to support the phylogenetic analysis and thereby defining essential motifs in OBP for protein-protein and protein-DNA interactions. The next study was focused on genetic recombination between different HSV-1 strains. We followed the propagation of HSV-1 in cells infected with one to three genotypes of HSV-1 and calculated the number of recombination events. We found evidence for Rad51 and Rad52 involvement in recombination of the unique long and unique short gene segments of HSV-1. We also observed an increased recombination rate in cells with retarded ligation of Okazaki-fragments. The fidelity of recombination in virus propagated through mixed infections appears to be high since expansion or shortening of repeated sequences in the US7 gene was not detected. In the third study we examined the replication-coupled transcription of HSV-1 late genes, which are known to depend on DNA replication for efficient expression. Using chromatin immuno-precipitation we could determine that recruitment of RNA polymerase II to late gene promoters occur even in the absence of replication. Recruitment was dependent on ICP4, but delayed in comparison with early gene promoters. These observations suggested the involvement of transcription elongation and/or maturation in the expression of gamma genes. By using the drug DRB, which inhibits the kinase CDK9, a component of the positive transcription elongation factor B, and siRNA against Spt5, a transcription processivity factor, we could show a specific impairment of late gene expression, with only minimal effect on early gene expression and DNA synthesis. We suggest that CDK9 and Spt5 are specifically recruited to replicated late genes and…

Subjects/Keywords: Herpes Simplex Virus 1; DNA replication; DNA recombination; Transcription

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

APA (6^th Edition):

Tang, K. (2015). Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/40883

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):

Tang, Ka-Wei. “Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription.” 2015. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 16, 2021. http://hdl.handle.net/2077/40883.

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

MLA Handbook (7^th Edition):

Tang, Ka-Wei. “Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription.” 2015. Web. 16 Apr 2021.

Vancouver:

Tang K. Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2015. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2077/40883.

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

Council of Science Editors:

Tang K. Herpes Simplex Virus 1 DNA replication and its role in recombination and transcription. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2015. Available from: http://hdl.handle.net/2077/40883

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

Tampere University

12. Malm, Maria. Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models .

Degree: 2011, Tampere University

URL: https://trepo.tuni.fi/handle/10024/66762

► Väitöskirjatyössä arvioitiin alun perin Tampereen yliopistossa ja myöhemmin FIT Biotech Oy:ssä kehitetyn HIV-1 rokotteen tehoa ja kykyä synnyttää HIV-spesifinen suojaava immuunivaste hiirimalleissa. Terapeuttisen HIV-1 rokotteen… (more)

▼ Väitöskirjatyössä arvioitiin alun perin Tampereen yliopistossa ja myöhemmin FIT Biotech Oy:ssä kehitetyn HIV-1 rokotteen tehoa ja kykyä synnyttää HIV-spesifinen suojaava immuunivaste hiirimalleissa. Terapeuttisen HIV-1 rokotteen tarkoituksena on herättää immuunipuolustus tuhoamaan elimistön HI-viruksen infektoimia soluja. Rokotteen osoitettiin tehokkaasti aktivoivan antigeenispesifisiä tappajasoluja ja herättävän suojaavan immuunivasteen kokeellisissa hiirimalleissa. Kehitetty geneettinen rokote, GTU®-MultiHIV, muodostaa multiantigeenin eli yhdistelmäproteiinin, joka koostuu HIV-1 Rev, Nef, Tat ja Gag p17/p24 -proteiineista ja T-solujen epitooppialueista. MultiHIV-proteiini tuotetaan elimistössä GTU® -vektorista, jonka on osoitettu muodostavan antigeeniä pidempikestoisesti ja tehokkaammin kuin perinteisten rokotevektoreiden. GTU®-MultiHIV immunisoinnin osoitettiin synnyttävän rokotespesifisen solu- ja vasta-ainevälitteisen immuunivasteen jokaista vektorin tuottamaa antigeeniä kohtaan. Immuunivasteen herättämisen osoitettiin olevan immunisaatioreitistä ja käytetystä annostuksesta riippuvainen, ihonsisäinen immunisointi todettiin lihaksensisäistä immunisaatiota tehokkaammaksi. Soluvälitteistä immuunivastetta arvioitiin immunisoitujen hiirien lymfosyyttien antigeenispesifisellä gamma interferonin erityksellä. HIV-spesifisen immuunivasteen suojatehoa arvioitiin kahdessa kokeellisessa hiirimallissa, joista ensimmäisessä mallissa arvioitiin immunisoinnin kykyä estää MultiHIV-antigeeniä kantavien kasvainsolujen lisääntymistä. Toisessa mallissa saatiin viitteitä rokotteen suojatehosta eri HIV-1 kantoja vastaan käyttämällä hiirien pseudovirusaltistukseen HIV-1 kantoja, jotka poikkesivat rokotteen HIV-1 antigeenien kannoista. Lopuksi tutkittiin dendriittisolujen oleellista merkitystä immuunivasteen syntymisessä GTU®-MultiHIV DNA immunisoinnin jälkeen uutta lähestymistapaa käyttäen.; HIV-1 vaccine development has proven an extremely challenging task, largely related to the highly variable nature of the virus which generates constantly new variants able to escape the immune system surveillance and lack of correlates of protection. DNA vaccines have the potential to encode multiple viral antigens, thereby eliciting immune responses that could lead to improved containment of the HIV-1 virus in a relatively safe way. Furthermore, the endogenous synthesis of the plasmid encoded antigen mimics the viral replication and enables the antigen presentation in a natural way for immune system cells. The first aim of this study was to evaluate the immunogenicity of the HIV-1 multigene DNA plasmid vaccine, encoding for Rev, Nef, Tat, p17, p24 and selected T cell epitopes of HIV-1 pol and env in mice. GTU® vector encoding the multigene is an advanced expression vector resulting in higher expression level and longer maintenance of the plasmid in dividing cells compared to conventional DNA plasmids. In the first part of the work, we demonstrated that GTU®-MultiHIV DNA induces cellular and humoral immune responses in mice directed to all…

Subjects/Keywords: HIV-1 ; plasmidi-DNA rokote ; hiirimalli ; DNA plasmid vaccine ; murine model

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

APA (6^th Edition):

Malm, M. (2011). Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models . (Doctoral Dissertation). Tampere University. Retrieved from https://trepo.tuni.fi/handle/10024/66762

Chicago Manual of Style (16^th Edition):

Malm, Maria. “Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models .” 2011. Doctoral Dissertation, Tampere University. Accessed April 16, 2021. https://trepo.tuni.fi/handle/10024/66762.

MLA Handbook (7^th Edition):

Malm, Maria. “Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models .” 2011. Web. 16 Apr 2021.

Vancouver:

Malm M. Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models . [Internet] [Doctoral dissertation]. Tampere University; 2011. [cited 2021 Apr 16]. Available from: https://trepo.tuni.fi/handle/10024/66762.

Council of Science Editors:

Malm M. Assessing the Immunogenicity of GTU®-based HIV-1 Multigene DNA Vaccines in Murine Models . [Doctoral Dissertation]. Tampere University; 2011. Available from: https://trepo.tuni.fi/handle/10024/66762

University of Cambridge

13. Trigg, Benjamin James. An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs.

Degree: PhD, 2019, University of Cambridge

URL: https://doi.org/10.17863/CAM.32141 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763774

► DNA damage response (DDR) pathways are essential in maintaining genomic integrity in cells, but many DDR proteins have other important functions such as in the… (more)

▼ DNA damage response (DDR) pathways are essential in maintaining genomic integrity in cells, but many DDR proteins have other important functions such as in the innate immune sensing of cytoplasmic DNA. Some DDR proteins are known to be beneficial or restrictive to viral infection, but most remain uncharacterised in this respect. Non-homologous end joining (NHEJ) is a mechanism of double stranded DNA (dsDNA) repair that functions to rapidly mend broken DNA ends. The NHEJ machinery is well characterised in the context of DDR but recent studies have linked the same proteins to innate immune DNA sensing and, hence, anti-viral responses. The aim of this thesis is to further investigate the interplay between herpes simplex virus 1 (HSV-1), a dsDNA virus, and two NHEJ proteins, DNA protein kinase catalytic subunit (DNA-PKcs) and paralogue of XRCC4 and XLF (PAXX). PAXX was first described in the literature as a NHEJ protein in 2015, but whether it has any role in the regulation of virus infection has not been established. Here we show that PAXX acts as a restriction factor for HSV-1 because PAXX-/- (KO) cells produce a consistently higher titre of HSV-1 than the respective wild type (WT) cells. We hypothesised that this could be due to a role of PAXX binding viral DNA and directly inhibiting HSV-1 replication or activating an anti-viral innate immune response. We have been able to, at least partially, rule out both of these initial hypotheses by showing that there was a reduced number of viral genomes present in KO cells during active lytic infection, and that an identical level of type I interferons are produced from WT and KO cells during HSV-1 infection. Although further characterisation of HSV-1 infection in WT and KO cells has not defined the molecular mechanism of restriction of HSV-1 by PAXX, we have uncovered a potential role for PAXX in mitogen-activated protein kinase (MAPK) signalling. In addition, and consistent with its function in restriction of HSV-1 infection, we show that infection with this virus in WT cells induces a loss of nuclear PAXX protein. Preliminary data suggest that these changes in localisation may occur as a result of stimulation of the cells with DNA, but not the RNA analogue poly(I:C). The role of PAXX in the regulation of HSV-1 infection in vivo was investigated by studying KO mice. Despite previous observations that mice lacking NHEJ proteins have brain defects related to autoinflammatory pathology, there were no obvious defects in the development of Paxx-/- mice, and they had brains of normal weight. No significant difference in viral spread or viral protein expression was observed between WT and KO HSV-1 infected mice, and KO mice did not exhibit abnormal pathology. There were, however, small but significant differences in the cellular immune response to infection which might be explained by reduced MAPK signalling in KO cells. DNA-PKcs is another component of the NHEJ machinery that acts to assist in dsDNA break repair in the nucleus and as an innate sensor of cytoplasmic viral DNA, but…

Subjects/Keywords: 572.8; DNA damage; HSV-1; PAXX; DNA-PKcs; Innate immunity

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APA (6^th Edition):

Trigg, B. J. (2019). An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.32141 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763774

Chicago Manual of Style (16^th Edition):

Trigg, Benjamin James. “An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs.” 2019. Doctoral Dissertation, University of Cambridge. Accessed April 16, 2021. https://doi.org/10.17863/CAM.32141 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763774.

MLA Handbook (7^th Edition):

Trigg, Benjamin James. “An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs.” 2019. Web. 16 Apr 2021.

Vancouver:

Trigg BJ. An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs. [Internet] [Doctoral dissertation]. University of Cambridge; 2019. [cited 2021 Apr 16]. Available from: https://doi.org/10.17863/CAM.32141 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763774.

Council of Science Editors:

Trigg BJ. An exploration of the interplay between HSV-1 and the non-homologous end joining proteins PAXX and DNA-PKcs. [Doctoral Dissertation]. University of Cambridge; 2019. Available from: https://doi.org/10.17863/CAM.32141 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.763774

University of Toronto

14. Mateo, Abigail Rachele. The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline.

Degree: PhD, 2018, University of Toronto

URL: http://hdl.handle.net/1807/89703

► The production of gametes with the correct genome content relies on the formation of crossovers (CO) during meiosis. This involves the deliberate creation of programmed… (more)

Subjects/Keywords: BRC-1; BRCA1; CEP-1; DNA repair; meiosis; p53; 0369

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APA (6^th Edition):

Mateo, A. R. (2018). The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89703

Chicago Manual of Style (16^th Edition):

Mateo, Abigail Rachele. “The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline.” 2018. Doctoral Dissertation, University of Toronto. Accessed April 16, 2021. http://hdl.handle.net/1807/89703.

MLA Handbook (7^th Edition):

Mateo, Abigail Rachele. “The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline.” 2018. Web. 16 Apr 2021.

Vancouver:

Mateo AR. The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline. [Internet] [Doctoral dissertation]. University of Toronto; 2018. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1807/89703.

Council of Science Editors:

Mateo AR. The p53-like Protein CEP-1 is Required for Meiotic Fidelity in the C. elegans Germline. [Doctoral Dissertation]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89703

University of Michigan

15. Mazurkiewicz-Munoz, Anna M. Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2.

Degree: PhD, Molecular biology, 2005, University of Michigan

URL: http://hdl.handle.net/2027.42/125443

► Activation of the tyrosine kinase JAK2 is an essential step in signaling by growth hormone (GH) and other ligands of the cytokine family of receptors.… (more)

▼ Activation of the tyrosine kinase JAK2 is an essential step in signaling by growth hormone (GH) and other ligands of the cytokine family of receptors. To gain insight into how JAK2 contributes to cellular responses to ligand, I looked for novel JAK2 regulatory sites and binding proteins. This work identifies phosphorylated serine 523 (Ser 523) in JAK2 as a negative regulatory site of JAK2 kinase activity. Ser 523 is rapidly but transiently phosphorylated in response to GH. MEK1 inhibitor suppresses GH-dependent phosphorylation of JAK2 at Ser 523, suggesting that ERKs 1 and/or 2 phosphorylate Ser 523 in response to GH. Other activators of ERKs, phorbol 12-myristate 13-acetate (PMA) and epidermal growth factor, stimulate phosphorylation of Ser 523. Mutation of Ser 523 to alanine enhances GH-dependent tyrosyl phosphorylation of JAK2 and STAT5, suggesting that phosphorylation of Ser 523 inhibits JAK2 kinase activity. Thus, phosphorylation of Ser 523 by ERKs 1/2 in JAK2 may act in a negative feedback manner to dampen the initial activation of JAK2 in response to GH and provide a mechanism by which prior exposure to ERK activating ligands might dampen the cellular response to GH. I also used the yeast two-hybrid system to identify steroid sensitive gene 1 (SSG1) as a novel JAK2 binding protein. I provide evidence that SSG1 binds preferentially to the active form of JAK2, is phosphorylated by JAK2, and localizes to the nucleus, perinuclear region and the plasma membrane. SSG1 inhibits GH-induced expression of the c-fos gene, suggesting that SSG1 is a signaling protein involved in GH regulation of gene transcription. Furthermore, I identified an SRPX5 domain in SSG1 as a novel JAK2 interaction domain. This domain is common to a newly emerging group of proteins that includes rat SSG1/CL2/DRO1, its mouse and human homolog upregulated in BRS-3 deficient mice (Urb), chicken ortholog Equarin, and SRPX/drs/ETX1 and SRPUL. The SRPX5 domain is both necessary and sufficient for binding to JAK2 in a phosphotyrosine dependent manner and may therefore be a novel protein-protein, possibly phosphotyrosine binding, interaction domain. Taken together, this work provides important insight into signaling mechanisms used by the cytokine receptor family by identifying a binding partner and regulatory site in JAK2, both of which inhibit its ability to activate cytokine signaling pathways. Advisors/Committee Members: Carter-Su, Christin (advisor).

Subjects/Keywords: Binding; Cytokine Receptor-associated Tyrosine Kinase; Function; Identification; Inhibit; Jak2; Partner; Regulatory; Site; Steroid-sensitive Gene 1; Tyrosyl Phosphorylation

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APA (6^th Edition):

Mazurkiewicz-Munoz, A. M. (2005). Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/125443

Chicago Manual of Style (16^th Edition):

Mazurkiewicz-Munoz, Anna M. “Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2.” 2005. Doctoral Dissertation, University of Michigan. Accessed April 16, 2021. http://hdl.handle.net/2027.42/125443.

MLA Handbook (7^th Edition):

Mazurkiewicz-Munoz, Anna M. “Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2.” 2005. Web. 16 Apr 2021.

Vancouver:

Mazurkiewicz-Munoz AM. Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2. [Internet] [Doctoral dissertation]. University of Michigan; 2005. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2027.42/125443.

Council of Science Editors:

Mazurkiewicz-Munoz AM. Identification of a binding partner and regulatory site that inhibit the function of the cytokine receptor -associated tyrosine kinase JAK2. [Doctoral Dissertation]. University of Michigan; 2005. Available from: http://hdl.handle.net/2027.42/125443

Texas Tech University

16. Grandjean, Carter Jules. The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues.

Degree: Chemistry, 1968, Texas Tech University

URL: http://hdl.handle.net/2346/18511

Subjects/Keywords: Ovalbumin; Tyrosyl residues

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

APA (6^th Edition):

Grandjean, C. J. (1968). The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues. (Thesis). Texas Tech University. Retrieved from http://hdl.handle.net/2346/18511

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):

Grandjean, Carter Jules. “The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues.” 1968. Thesis, Texas Tech University. Accessed April 16, 2021. http://hdl.handle.net/2346/18511.

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

MLA Handbook (7^th Edition):

Grandjean, Carter Jules. “The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues.” 1968. Web. 16 Apr 2021.

Vancouver:

Grandjean CJ. The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues. [Internet] [Thesis]. Texas Tech University; 1968. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2346/18511.

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

Council of Science Editors:

Grandjean CJ. The reaction of N-acetylimidazole with denatured ovalbumin: and the determination of exposed tyrosyl residues. [Thesis]. Texas Tech University; 1968. Available from: http://hdl.handle.net/2346/18511

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

17. Watson, Ryan A. Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy.

Degree: PhD, Chemistry and Biochemistry, 2018, Georgia Tech

URL: http://hdl.handle.net/1853/61665

► Ribonucleotide reductase (RNR) catalyzes the production of deoxyribonucleotides in all cells. In E. coli class Ia RNR, a transient 2β2 complex forms when a ribonucleotide… (more)

Subjects/Keywords: Ribonucleotide reductase; FTIR spectroscopy; Tyrosyl radical

10 more images…

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APA (6^th Edition):

Watson, R. A. (2018). Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/61665

Chicago Manual of Style (16^th Edition):

Watson, Ryan A. “Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy.” 2018. Doctoral Dissertation, Georgia Tech. Accessed April 16, 2021. http://hdl.handle.net/1853/61665.

MLA Handbook (7^th Edition):

Watson, Ryan A. “Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy.” 2018. Web. 16 Apr 2021.

Vancouver:

Watson RA. Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy. [Internet] [Doctoral dissertation]. Georgia Tech; 2018. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1853/61665.

Council of Science Editors:

Watson RA. Identification of redox-linked structural changes in ribonucleotide reductase (RNR) by way of reaction-induced FTIR spectroscopy. [Doctoral Dissertation]. Georgia Tech; 2018. Available from: http://hdl.handle.net/1853/61665

18. Κωνσταντινόπουλος, Αγγελής. Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία.

Degree: 2009, University of Patras

URL: http://nemertes.lis.upatras.gr/jspui/handle/10889/1741

►

Σκοπός: Να διερευνηθεί η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε άνδρες με στυτική δυσλειτουργία. Μέθοδοι: Ασθενείς πάνω από… (more)

▼

Σκοπός: Να διερευνηθεί η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε άνδρες με στυτική δυσλειτουργία. Μέθοδοι: Ασθενείς πάνω από 18 ετών με στυτική δυσλειτουργία αγγειακής αιτιολογίας για πάνω από 6 μήνες, είτε μόνη είτε σε συνδυασμό με νοσολογικές καταστάσεις ισχυρά συσχετιζόμενες με ενδοθηλιακή δυσλειτουργία όπως σακχαρώδης διαβήτης/μεταβολικό σύνδρομο, υπέρταση και στεφανιαία νόσος, έλαβαν σιλδεναφίλη 25 mg ημερησίως από του στόματος για 4 εβδομάδες. Δείκτες της ενδοθηλιακής λειτουργίας μετρήθηκαν στο πλάσμα στην αρχή και το τέλος της θεραπείας χρησιμοποιώντας τυπικές μεθόδους και εμπορικά διαθέσιμα υλικά. Αποτελέσματα: 112 άνδρες με μέση ηλικία (SD) 60,6 (7,3) έτη ολοκλήρωσαν το θεραπευτικό πρωτόκολλο. Η χορήγηση 25 mg σιλδεναφίλης καθημερινά για 4 εβδομάδες μείωσε σημαντικά τα επίπεδα της ενδοθηλίνης-1 σε σύγκριση με την αρχή της θεραπείας (2,83 ± 1,63 έναντι 3,24 ± 1,90 pg/ml, p<0,001). Σημαντικές αλλαγές παρατηρήθηκαν επίσης για το οξείδιο του αζώτου (ΝΟ) (35,12 ± 21,14 έναντι 31,91 ± 16,28 pmol/lt, p=0,01), τα επίπεδα της cGMP (3,79 ± 2,37 έναντι 2,70 ± 1.34 pmol/ml, p<0,001) και τον παράγοντα von Willebrand (956,08 ± 514,25 έναντι 1007,42 ± 466,25 mU/ml) αλλά όχι και για τους άλλους δείκτες που μετρήθηκαν (θρομβομοδουλίνη και Ε-σελεκτίνη). Η στυτική λειτουργία βελτιώθηκε επίσης. Συμπεράσματα: Η σιλδεναφίλη σε καθημερινή χορήγηση βελτιώνει την ενδοθηλιακή λειτουργία όπως αυτή εκτιμάται με τα επίπεδα βιολογικών δεικτών σε ασθενείς με στυτική δυσλειτουργία. Αυτά τα αποτελέσματα συμφωνούν με άλλες μελέτες που δείχνουν όμοια αποτελέσματα με θεραπεία με αναστολείς της φωσφοδιεστεράσης 5. Η κλινική σημασία των αποτελεσμάτων αυτών χρήζει περαιτέρω διερεύνησης.

Objective: To investigate the impact of daily sildenafil on levels of soluble molecular markers of endothelial function in men with erectile dysfunction. Methods: Patients over 18 years of age with erectile dysfunction of vascular aetiology for more than 6 months, either alone or in combination with disease states strongly associated with endothelial dysfunction such as diabetes/metabolic syndrome, hypertension and coronary artery disease, received sildenafil 25 mg orally for 4 weeks. Markers of endothelial function were measured in plasma at baseline and end-of-treatment using standard methods and commercially available kits. Results: 112 men with mean (SD) age of 60.6 (7.3) years completed the protocol. Sildenafil 25mg daily for 4 weeks significantly reduced endothelin-1 levels compared to baseline (2.83 ± 1.63 vs. 3.24 ± 1.90 pg/ml, p<0.001). Significant changes were also observed for nitric oxide (35.12 ± 21.14 vs. 31.91 ± 16.28 pmol/lt, p=0.01) and cyclic guanosine monophosphate (3.79 ± 2.37 vs. 2.70 ± 1.34 pmol/ml, p<0.001) and von Willebrand factor (956.08 ± 514.25 vs. 1007.42 ± 466.25 mU/ml) levels but not for the other biomarkers measured (thrombomodulin and E-selectin). Erectile function was significantly improved. Conclusions: Daily sildenafil improves endothelial function as…

Advisors/Committee Members: Περιμένης, Πέτρος, Konstantinopoulos, Angelis, Περιμένης, Πέτρος, Σπάθας, Διονύσιος, Αθανασόπουλος, Αναστάσιος, Αναστασίου, Ευάγγελος, Σπυρόπουλος, Κωνσταντίνος, Γυφτόπουλος, Κωνσταντίνος, Γιαννίτσας, Κωνσταντίνος.

Subjects/Keywords: Σιλδεναφίλη; Ενδοθηλιακή δυσλειτουργία; Στυτική δυσλειτουργία; Μοριακοί δείκτες; Ενδοθήλιο; Ενδοθηλιακή λειτουργία; Αναστολείς φωσφοδιεστεράσης 5; 616.692 206 1; Sildenafil; Endothelial dysfunction; Erectile dysfunction; Molecular markers; Endothelium; Endothelial function; Phosphodiesterase 5 inhibitors

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APA (6^th Edition):

Κωνσταντινόπουλος, �. (2009). Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία. (Doctoral Dissertation). University of Patras. Retrieved from http://nemertes.lis.upatras.gr/jspui/handle/10889/1741

Chicago Manual of Style (16^th Edition):

Κωνσταντινόπουλος, Αγγελής. “Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία.” 2009. Doctoral Dissertation, University of Patras. Accessed April 16, 2021. http://nemertes.lis.upatras.gr/jspui/handle/10889/1741.

MLA Handbook (7^th Edition):

Κωνσταντινόπουλος, Αγγελής. “Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία.” 2009. Web. 16 Apr 2021.

Vancouver:

Κωνσταντινόπουλος �. Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία. [Internet] [Doctoral dissertation]. University of Patras; 2009. [cited 2021 Apr 16]. Available from: http://nemertes.lis.upatras.gr/jspui/handle/10889/1741.

Council of Science Editors:

Κωνσταντινόπουλος �. Η επίδραση της καθημερινής χορήγησης σιλδεναφίλης στα επίπεδα πλάσματος διαλυτών δεικτών της ενδοθηλιακής λειτουργίας σε ασθενείς με στυτική δυσλειτουργία. [Doctoral Dissertation]. University of Patras; 2009. Available from: http://nemertes.lis.upatras.gr/jspui/handle/10889/1741

University of Gothenburg / Göteborgs Universitet

19. Olausson, Josefin. Studies on microcirculation in insulin resistance.

Degree: 2015, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/39546

► The overall aim of this thesis was to investigate the microcirculation in insulin resistance, with focus on the expression of endothelin-1, through a translational approach.… (more)

▼ The overall aim of this thesis was to investigate the microcirculation in insulin resistance, with focus on the expression of endothelin-1, through a translational approach. Specific aims: 1) Investigate if circulating endothelin-1 levels predicts incident coronary heart disease events. 2) To assess if sex differences modify endothelin-1 as a predictor of type 2 diabetes. 3) To investigate if microvascular insulin resistance impairs insulin delivery to the subcutaneous adipose tissue and skeletal muscle. 4) To investigate if acute administration of the PDE-5 inhibitor tadalafil induces positive vascular, metabolic and anti-inflammatory effects in type 2 diabetes. 5) To further elucidate the molecular action of tadalafil in tumour necrosis factor-α (TNF-α) stimulated human endothelial cells. Principal findings: The population-based cohort in Vara-Skövde was investigated for paper I-II. During baseline cardiovascular risk factors and endothelin-1 were assessed and incident coronary heart disease (CHD) was followed-up during a 10-year period (paper I). Endothelin-1 levels had a predictive value for incident CHD in women, but not in men. A randomly selected subgroup was investigated in a follow-up after 10 years, and impaired glucose tolerance (IGT) and T2D was documented for paper II. Here, higher quartiles of endothelin-1 at baseline were associated with IGT/T2D at follow-up in women. Paper III investigates microvascular aspects of insulin resistance using microdialyis; participants with T2D and age-matched healthy controls were studied after an oral glucose load. Participants with T2D had decreased delivery of insulin to adipose tissue, and a blunted subcutaneous adipose tissue blood flow compared with controls. In paper IV, T2D participants received either placebo or tadalafil (20 mg) before a mixed meal in a randomized controlled trial. Tadalafil increased forearm blood flow, glucose uptake and capillary recruitment, and blunted a postprandial increase of endothelin-1. In paper V, the effects of tadalafil were studied in an experimental setting using TNF-α stimulated endothelial cells. Tadalafil treatment decreased expression of c-Jun N-terminal kinase (JNK) phosphorylation as well as reduced gene expression and secretion of endothelin-1. Conclusions: This thesis shows that (i) endothelial dysfunction precedes IGT/T2D and CHD, and that endothelin-1 may pose as a risk factor for women, (ii) delivery of insulin from the circulation to subcutaneous adipose tissue is impaired in participants with T2D, and that participants with T2D exhibit a blunted postprandial blood flow response, (iii) acute administration of tadalafil induces positive vascular and metabolic effects in the postprandial state in T2D, and tadalafil decrease gene expression of endothelin-1 in cultured endothelial cells by decreasing activation of JNK.

Subjects/Keywords: endothelin-1; type 2 diabetes; coronary heart disease; phosphodiesterase-5 inhibition; tadalafil; insulin resistance; endothelial dysfunction; c-Jun N-terminal kinase; nitric oxide; microdialysis

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

APA (6^th Edition):

Olausson, J. (2015). Studies on microcirculation in insulin resistance. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/39546

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):

Olausson, Josefin. “Studies on microcirculation in insulin resistance.” 2015. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed April 16, 2021. http://hdl.handle.net/2077/39546.

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

MLA Handbook (7^th Edition):

Olausson, Josefin. “Studies on microcirculation in insulin resistance.” 2015. Web. 16 Apr 2021.

Vancouver:

Olausson J. Studies on microcirculation in insulin resistance. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2015. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2077/39546.

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

Council of Science Editors:

Olausson J. Studies on microcirculation in insulin resistance. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2015. Available from: http://hdl.handle.net/2077/39546

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

Louisiana State University

20. Yang, Yanling. Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus.

Degree: PhD, 2011, Louisiana State University

URL: etd-08042011-230059 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3092

► Klenow and Klentaq are the “large fragments” of the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus. Examination of the DNA binding thermodynamics… (more)

▼ Klenow and Klentaq are the “large fragments” of the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus. Examination of the DNA binding thermodynamics of both polymerases to replication versus repair substrates shows that Klenow binds primed-template DNA with up to 50X higher affinity than it binds to a nicked DNA, gapped DNAs, DNA with blunt-end or a 3’ overhang, while Klentaq binds all of these DNAs similarly. The presence of 5’ or 3’ phosphates has slightly different effects on DNA binding by both polymerases. In contrast, both polymerases bind mismatched DNA tighter than matched DNA, suggesting that they may share a similar mechanism to identify mismatched DNA, despite the lack of proofreading ability in Klentaq. The effects of Klenow and Klentaq on ligation of DNA ligase were also studied. Both polymerases stimulate the intermolecular ligation activity of E. coli DNA ligase at concentrations sub-stoichiometric to the DNA concentration. This effect occurs with E. coli DNA ligase, but not for T4 and Taq ligases. Additionally, neither polymerase significantly enhances ligation of a substrate containing a single nick, suggesting that the polymerases bridge the two DNA ends during intermolecular ligation. The nucleotide incorporation activities of both polymerases on substrates minicing double-strand breaks (DSBs) were also examined. Both proteins are able to “repair” DSBs via alignment-based strand-displacement DNA synthesis. Moreover, their repair abilities have different dependences on 5’ phosphate and DNA ligase when DSBs contain non-cohesive ends. Additionally, both proteins mediated palindrome amplification alone when the short inverted repeats occur near DNA breaks, suggesting that short inverted repeats in prokaryotes may help in DSB repair. 5’ phosphate at the matched break end is required for DSBs repair by both polymerases when one break end contains 3 consecutive mismatches. Results of the electrophoretic mobility shift assay show that Klenow-DNA complexes are observed as slow or fast moving bands, or both while all Klentaq-DNA complexes are observed as slow moving bands. The protection of both ends of a DNA by Klenow from exonuclease digestion suggests that the slow moving bands may correspond to the 2:1 polymerase-DNA complex.

Subjects/Keywords: Klenow; Klentaq; DNA Binding; Protein-DNA Interaction; Gapped DNA; DNA Double-strand Break Repair; Mismatched DNA; Stimulation on Ligase; 2:1 Polymerase-DNA complex

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

APA (6^th Edition):

Yang, Y. (2011). Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus. (Doctoral Dissertation). Louisiana State University. Retrieved from etd-08042011-230059 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3092

Chicago Manual of Style (16^th Edition):

Yang, Yanling. “Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus.” 2011. Doctoral Dissertation, Louisiana State University. Accessed April 16, 2021. etd-08042011-230059 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3092.

MLA Handbook (7^th Edition):

Yang, Yanling. “Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus.” 2011. Web. 16 Apr 2021.

Vancouver:

Yang Y. Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus. [Internet] [Doctoral dissertation]. Louisiana State University; 2011. [cited 2021 Apr 16]. Available from: etd-08042011-230059 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3092.

Council of Science Editors:

Yang Y. Thermodynamics of DNA binding and break repair by the Pol I DNA polymerases from Escherichia coli and Thermus aquaticus. [Doctoral Dissertation]. Louisiana State University; 2011. Available from: etd-08042011-230059 ; https://digitalcommons.lsu.edu/gradschool_dissertations/3092

Johannes Gutenberg Universität Mainz

21. Meise, Ruth Hildegard. Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress.

Degree: 2014, Johannes Gutenberg Universität Mainz

URL: http://ubm.opus.hbz-nrw.de/volltexte/2014/3887/

► Die mittlere Überlebenszeit nach Erkennung eines Glioblastoms ohne Behandlung liegt bei 3 Monaten und kann durch die Behandlung mit Temozolomid (TMZ) auf etwa 15 Monate… (more)

▼ Die mittlere Überlebenszeit nach Erkennung eines Glioblastoms ohne Behandlung liegt bei 3 Monaten und kann durch die Behandlung mit Temozolomid (TMZ) auf etwa 15 Monate gesteigert werden. Neben TMZ sind die chlorethylierenden Nitrosoharnstoffe die meistversprechendsten und am häufigsten eingesetzten Chemotherapeutika in der Gliomtherapie. Hier liegt die mittlere Überlebenszeit bei 17,3 Monaten. Um die Therapie des Glioblastoms noch effektiver zu gestalten und Resistenzen zu begegnen, werden unterschiedlichste Ansätze untersucht. Eine zentrale Rolle spielen hierbei das activator protein 1 (AP-1) und die mitogen aktivierten Proteinkinasen (MAPK), deren Funktion in bisherigen Arbeiten noch unzureichend beleuchtet wurde.rnBesonders mit der Rolle des AP-1-bildenden Proteins FRA-1 in der Therapie des Glioblastoms haben sich bisher nur wenige Arbeiten beschäftigt, weshalb im ersten Teil der vorliegenden Arbeit dessen Funktion in der Regulation der Chemosensitivität gegenüber dem chlorethylierenden Agenz ACNU genauer untersucht wurde. Es konnte gezeigt werden, dass die FRA 1-Expression durch Behandlung mit ACNU induziert wird. Die Induktion erfolgte über die beiden MAPKs ERK1/2 und p38K. JNK hatte keinen Einfluss auf die Induktion. Durch die Herunterregulation der FRA-1-Expression mit Hilfe von siRNA und eines shRNA exprimierenden Plasmids kam es zu einer signifikanten Sensitivierung gegenüber ACNU. Dabei konnte gezeigt werden, dass die Herunterregulation der FRA-1-Expression in einer verminderten AP 1-Bildung, bedingt durch eine reduzierte Menge an FRA-1 im AP-1-Komplex resultiert. Die Sensitivierung gegenüber ACNU ist weder durch eine Veränderung in der DNA-Reparatur, noch in der Modulation der FAS-Ligand- bzw. FAS-Rezeptor-Expression bedingt. Auch die hier untersuchten BCL 2-Familienmitglieder wiesen keine Unterschiede in der Expression durch Modulation der FRA 1-Expression auf. Allerdings kam es durch die verminderte FRA-1-Expression zu einer Reduktion der Zellzahl in der G2/M-Phase nach Behandlung mit ACNU. Diese ging einher mit einer reduzierten Menge an phosphoryliertem und unphosphoryliertem CHK1, weshalb davon auszugehen ist, dass FRA 1 nach ACNU-Behandlung in Gliomzellen vor der Apoptose schützt, indem es modulierend auf die Zellzykluskontrolle einwirkt.rnIm zweiten Teil dieser Arbeit wurde die Regulation der apoptotischen Antwort nach Behandlung mit ACNU und TMZ genauer beleuchtet, wobei ein spezielles Augen¬merk auf AP 1 und die MAPKs gelegt wurde. Hier konnte gezeigt werden, dass die Apoptose nach Behandlung mit ACNU bzw. TMZ sowohl durch Spaltung von Pro-Caspase 8, als auch Pro-Caspase 9 eingeleitet wird. Dabei akkumulierte in beiden Fällen p53 vermehrt im Zellkern. Eine Inhibierung der transkriptionellen Aktivität von p53 führte nach ACNU-Behandlung zu einer Sensitivierung der Zellen, nach TMZ-Behandlung kam es zu einem leichten Anstieg in der Vitälität. Der FAS-Rezeptor wurde nach ACNU- und nach TMZ-Behandlung aktiviert und auch die DNA-Reparaturproteine DDB2 und XPC wurden in beiden Fällen vermehrt…

Subjects/Keywords: FRA-1; MAPK; ACNU; Temozolomid; DNA-Reparatur; Apoptose; FRA-1; MAPK; ACNU, temozolomide; DNA repair; apoptosis; Life sciences

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

APA (6^th Edition):

Meise, R. H. (2014). Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress. (Doctoral Dissertation). Johannes Gutenberg Universität Mainz. Retrieved from http://ubm.opus.hbz-nrw.de/volltexte/2014/3887/

Chicago Manual of Style (16^th Edition):

Meise, Ruth Hildegard. “Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress.” 2014. Doctoral Dissertation, Johannes Gutenberg Universität Mainz. Accessed April 16, 2021. http://ubm.opus.hbz-nrw.de/volltexte/2014/3887/.

MLA Handbook (7^th Edition):

Meise, Ruth Hildegard. “Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress.” 2014. Web. 16 Apr 2021.

Vancouver:

Meise RH. Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress. [Internet] [Doctoral dissertation]. Johannes Gutenberg Universität Mainz; 2014. [cited 2021 Apr 16]. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2014/3887/.

Council of Science Editors:

Meise RH. Rolle der FOS-Proteine und des MAPK-Signallings in der Regulation der zellulären Antwort auf genotoxischen Stress. [Doctoral Dissertation]. Johannes Gutenberg Universität Mainz; 2014. Available from: http://ubm.opus.hbz-nrw.de/volltexte/2014/3887/

22. Camila André Pereira. Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina.

Degree: 2018, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-08112018-150821/

► O diabetes mellitus (DM) está associado a diversas complicações micro e macrovasculares diretamente relacionadas a doenças cardiovasculares. A prolongada exposição à hiperglicemia e a resistência… (more)

▼ O diabetes mellitus (DM) está associado a diversas complicações micro e macrovasculares diretamente relacionadas a doenças cardiovasculares. A prolongada exposição à hiperglicemia e a resistência a insulina são considerados os principais fatores envolvidos nestas complicações, as quais são exacerbadas pela disfunção endotelial. Mediadores inflamatórios contribuem potencialmente para o desenvolvimento de disfunção endotelial pela geração de espécies reativas de oxigênio (EROs) que, por sua vez, estimulam a transcrição de fatores pró- inflamatórios. Receptores específicos, como os NLRs (NOD-like receptors, receptores do tipo NOD) contribuem para instalação de processo inflamatório pela ativação do complexo inflamassoma. Este regula a ativação da caspase-1 e o processamento proteolítico dos precursores pró-IL-1? e pró-IL-18 nas citocinas maduras. Diversos mediadores podem ativar o inflamassoma NLRP3 como, por exemplo, EROs e DNA mitocondrial. Pouco é conhecido sobre o envolvimento de receptores NLRP3 e DNA mitocondrial na disfunção endotelial associada ao diabetes. Testamos a hipótese que a deficiência genética do receptor NLRP3 confere resistência à ativação de processo inflamatório na vasculatura de animais com diabetes tipo 1 (DM1) e, ainda, que DNA mitocondrial contribui para a ativação vascular do inflamassoma NLRP3 e para disfunção endotelial. Foram utilizados camundongos C57Bl/6 e deficientes para NLRP3, os quais foram tratados com veículo ou submetidos a protocolo para indução de DM1 com estreptozotocina. Parâmetros vasculares funcionais foram determinados em artérias mesentéricas de resistência. Células de músculo liso vascular (CMLV) e endoteliais foram utilizadas para avaliação da ativação do inflamassoma NLRP3 por DNA mitocondrial. A geração de EROs foi avaliada pela fluorescência para o dihidroetídio e pela quimiluminescência para lucigenina. A ativação de caspase-1 e IL-1? foi avaliada por western blot e o influxo de cálcio, por fluorescência. DNA mitocondrial foi avaliado pela expressão gênica de componentes da mitocôndria. O diabetes reduziu a vasodilatação dependente de endotélio, o que não ocorreu em artérias de animais deficientes de NLRP3. Animais diabéticos apresentaram aumento da expressão vascular do receptor NLRP3, da ativação de caspase-1 eIL-1? e da geração de EROs e peróxido de hidrogênio no leito mesentérico, eventos que ocorreram em menor intensidade em camundongos deficientes de NLRP3. Houve redução na expressão proteica vascular de Nox4 (NADPH oxidase 4), bem como na expressão gênica da molécula de adesão celular vascular-1 (VCAM-1, vascular cell adhesion molecule-1) e molécula de adesão intercelular-1 (ICAM-1, intercellular adhesion molecule-1) em animais deficientes de NLRP3. Houve aumento da liberação de DNA mitocondrial citosólico no pâncreas de animais diabéticos. A incubação com o DNA mitocondrial extraído do pâncreas de animais diabéticos promoveu ativação do inflamassoma em CMLV provenientes de animais C57Bl/6, mas não em CMLV provenientes de animais deficientes de NLRP3. Esta… Advisors/Committee Members: Rita de Cassia Aleixo Tostes Passaglia, Eliana Hiromi Akamine, Daniella Bonaventura, Carlos Renato Tirapelli.

Subjects/Keywords: diabetes tipo 1; disfunção endotelial; DNA mitocondrial; inflamassoma NLRP3; endothelial dysfunction; mitochondrial DNA; NLRP3 inflammasome; type 1 diabetes

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

APA (6^th Edition):

Pereira, C. A. (2018). Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina. (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/17/17133/tde-08112018-150821/

Chicago Manual of Style (16^th Edition):

Pereira, Camila André. “Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina.” 2018. Doctoral Dissertation, University of São Paulo. Accessed April 16, 2021. http://www.teses.usp.br/teses/disponiveis/17/17133/tde-08112018-150821/.

MLA Handbook (7^th Edition):

Pereira, Camila André. “Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina.” 2018. Web. 16 Apr 2021.

Vancouver:

Pereira CA. Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina. [Internet] [Doctoral dissertation]. University of São Paulo; 2018. [cited 2021 Apr 16]. Available from: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-08112018-150821/.

Council of Science Editors:

Pereira CA. Papel do inflamassoma NLRP3 nas alterações vasculares promovidas pelo diabetes tipo 1 em modelo induzido por estreptozotocina. [Doctoral Dissertation]. University of São Paulo; 2018. Available from: http://www.teses.usp.br/teses/disponiveis/17/17133/tde-08112018-150821/

23. Francisco André Marques de Oliveira Cariri. Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV).

Degree: 2014, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/87/87131/tde-08122014-110509/

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O presente projeto propõe a avaliação de respostas imunológicas induzidas por uma vacina de DNA bivalente para o controle de infecções por HIV e HSV.… (more)

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O presente projeto propõe a avaliação de respostas imunológicas induzidas por uma vacina de DNA bivalente para o controle de infecções por HIV e HSV. A vacina genética codifica a proteína gD do vírus HSV-1 geneticamente fusionada à proteína Gag (p24) do HIV, rica em epítopos reconhecidos por células T CD8+. A vacina de DNA pRE4p24 codifica a proteína p24 inserida em região próxima à porção C-terminal da proteína gD-1, permitindo que a proteína recombinante seja expressa na superfície da célula transfectada. A localização da proteína recombinante foi confirmada na superfície das células HEK-293T transfectadas por ensaios de imunofluorescência. Camundongos imunizados com a vacina foram capazes de gerar respostas de anticorpos específicos após três doses administradas pelas vias intramuscular (i.m.), intradérmica com seringa (i.d.) ou intradérmico por biobalística (gg). Foram analisadas as respostas imunológicas mediadas por linfócitos T CD8+ p24-específicas e, em função dos resultados obtidos, sendo a via i.m. escolhida como a mais promissora para os ensaios subsequentes. Na tentativa de aumentar a imunogenicidade da vacina, particularmente, para respostas celulares, foi avaliado o efeito da co-administração da formulação vacinal com outros plasmídeos que expressam citocinas (pIL-2, pIL-12 ou pGM-CSF), o teste de um vetor vacinal baseado no plasmídeo multicópia pVAX (pgDp24) e o emprego de um gene sintético para promover o aumento da expressão da proteína gD em células de mamíferos (pgDhp24). Por fim, desenvolvemos um modelo murino para a avaliação funcional de respostas citotóxicas antígeno-específicas a partir de uma linhagem tumoral capaz de expressar a proteína p24 do HIV. Camundongos Balb/c imunizados com o pgDp24 apresentaram um retardo no crescimento tumoral em relação aos animais não imunizados além de proteção parcial a desafios letais com HSV-1.

The present thesis aims to evaluate the immunological responses induced by a bivalent DNA vaccine to the control HIV and HSV infectious. This genetic vaccine codes the gD protein from the HSV-1 virus envelope genetically fused with HIV Gag (p24) protein, which has various epitopes recognized by human and murine T CD8+ cells. The DNA vaccine, named pRE4p24, codes for p24 protein, inserted close to the C-terminal region of gD-1 protein, leading to the expression of the recombinant protein on the surface of the transfected cells. The location of the recombinant protein was confirmed with transfected HEK-293 cellsby immunofluorescence assays. Mice immunized with the vaccine generated antigen-specific antibody responses after three doses administered intramuscularly (i.m), intradermally with a syringe (i.d) or intradermally by gene gun (bioballistic) (gg). The immunological responses mediated by specific-T CD8+ p24 lymphocytes were evaluated and, according to the data obtained, the i.m administration was chosen for the next assays. Aiming the improvement of the vaccine immunogenicity, particularly for cellular responses, the effect of co-administration with…

Advisors/Committee Members: Luis Carlos de Souza Ferreira, Andrea Balan Fernandes, Eliane Namie Miyaji, Enrique Mario Boccardo Pierulivo, Armando Morais Ventura.

Subjects/Keywords: Glicoproteína D; HIV; HSV-1; p24; Vacinas; Vacinas de DNA; DNA vacines; Glycoprotein D; HIV; HSV-1; p24; Vaccines

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

APA (6^th Edition):

Cariri, F. A. M. d. O. (2014). Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV). (Doctoral Dissertation). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/87/87131/tde-08122014-110509/

Chicago Manual of Style (16^th Edition):

Cariri, Francisco André Marques de Oliveira. “Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV).” 2014. Doctoral Dissertation, University of São Paulo. Accessed April 16, 2021. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-08122014-110509/.

MLA Handbook (7^th Edition):

Cariri, Francisco André Marques de Oliveira. “Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV).” 2014. Web. 16 Apr 2021.

Vancouver:

Cariri FAMdO. Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV). [Internet] [Doctoral dissertation]. University of São Paulo; 2014. [cited 2021 Apr 16]. Available from: http://www.teses.usp.br/teses/disponiveis/87/87131/tde-08122014-110509/.

Council of Science Editors:

Cariri FAMdO. Construção e caracterização imunológica de formulação vacinal com propriedade profiláticas voltada para o controle do vírus da imunodeficiência humana (HIV) e do vírus herpes (HSV). [Doctoral Dissertation]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/87/87131/tde-08122014-110509/

Univerzitet u Beogradu

24. Tolić, Anja Z., 1988- 33400935. Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK.

Degree: Biološki fakultet, 2020, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:20881/bdef:Content/get

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Biologija - Molekularna biologija / Biology - Molecular biology

Važan aspekt u rasvetljavanju procesa demetilacije DNK predstavlja identifikacija faktora koji regulušu aktivnost TET proteina. Cilj… (more)

Subjects/Keywords: TET1; TET2; PARP-1; PAR polymers; PARylation; DNA methylation; DNA demethylation; Cxcl12 gene

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

APA (6^th Edition):

Tolić, Anja Z., 1. 3. (2020). Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:20881/bdef:Content/get

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):

Tolić, Anja Z., 1988- 33400935. “Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK.” 2020. Thesis, Univerzitet u Beogradu. Accessed April 16, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:20881/bdef:Content/get.

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

MLA Handbook (7^th Edition):

Tolić, Anja Z., 1988- 33400935. “Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK.” 2020. Web. 16 Apr 2021.

Vancouver:

Tolić, Anja Z. 13. Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK. [Internet] [Thesis]. Univerzitet u Beogradu; 2020. [cited 2021 Apr 16]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:20881/bdef:Content/get.

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

Council of Science Editors:

Tolić, Anja Z. 13. Funkcionalna analiza interakcija TET-posredovane oksidacije 5-metilcitozina i PARP-zavisne ADP-ribozilacije u procesu demetilacije DNK. [Thesis]. Univerzitet u Beogradu; 2020. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:20881/bdef:Content/get

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

University of Illinois – Urbana-Champaign

25. Hsiao, Kuei-Yang. A histone H4 code regulates 53BP1-mediated responses to DNA damage.

Degree: PhD, 0325, 2012, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/29532

► Individual histone post-translational modifications have been implicated in regulating many cellular events. Modifications can occur at high densities in the N-terminal tail domains of core… (more)

▼ Individual histone post-translational modifications have been implicated in regulating many cellular events. Modifications can occur at high densities in the N-terminal tail domains of core histones, enabling the possibility that combinations of modifications regulate chromatin processes differently than modifications occurring individually. However, surprisingly little is known about the nature and functions of multi-site histone modification. This study investigates functional interactions between acetylation of lysine 16 (K16ac) and methylation of lysine 20 (K20me), two modifications that frequently occur together on molecules of histone H4 (H4). Methylation state-specific binding of the P53-binding protein 1 (53BP1) to dimethyl K20 H4 (K20me2) and the formation of 53BP1 nuclear foci near double strand breaks are early events in DNA damage responses (DDR) that provide a platform for the assembly of downstream effectors. Since global levels of K20me2 are relatively stable and are established independently of DNA damage, we propose that reversible changes in the levels of K16ac co-modification act like a dynamic switch to modulate DDR responses mediated by K20me2. Analyses of the interaction of the K20me2 binding domain of 53BP1 with H4 peptides in vitro reveal that K16ac co-modification attenuates specific recognition of K20me1/2 (mono- and di-methylation) by 53BP1. The possibility that K16ac and K20me2 interact functionally in vivo is demonstrated by my finding that K16 deacetylation accompanies the induction of H2A.X phosphorylation, a well-known marker for DDR, following DNA damage by either UV irradiation, hydroxyurea or bleocin treatment. Moreover, the effects of expressing K16 mutants of H4 and inhibition of histone deacetylases on 53BP1 foci formation induced by DNA damage support the hypothesis that K16ac co-modification negatively regulates the formation of 53BP1 foci. The functional significance of these interactions is underscored by the finding that K16 hyperacetylation also hindered 53BP1-mediated nonhomologous end-joining as demonstrated by treatment of HDACi and overexpression of a H4 mutant mimicking acetylation at K16. DNA damage-induced deacetylation was associated with transcriptional repression, but was not linked to chromatin decondensation. Deregulated DDR mechanisms are frequently involved in the development and progression of cancer, and interruption of the DDR is used in chemotherapeutic treatments against cancer. Further investigation of the role of H4 modifications in DDR will enhance our understanding of how genome integrity is maintained in normal cells and may provide insights crucial for developing new cancer therapies. Advisors/Committee Members: Mizzen, Craig A. (advisor), Bagchi, Milan K. (committee member), Kemper, Byron W. (committee member), Nardulli, Ann M. (committee member), Spies, Maria (committee member).

Subjects/Keywords: DNA damage; P53-binding protein 1 (53BP1); histone H4; methylation; acetylation; deacetylation; Deoxyribonucleic acid (DNA)

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APA (6^th Edition):

Hsiao, K. (2012). A histone H4 code regulates 53BP1-mediated responses to DNA damage. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/29532

Chicago Manual of Style (16^th Edition):

Hsiao, Kuei-Yang. “A histone H4 code regulates 53BP1-mediated responses to DNA damage.” 2012. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 16, 2021. http://hdl.handle.net/2142/29532.

MLA Handbook (7^th Edition):

Hsiao, Kuei-Yang. “A histone H4 code regulates 53BP1-mediated responses to DNA damage.” 2012. Web. 16 Apr 2021.

Vancouver:

Hsiao K. A histone H4 code regulates 53BP1-mediated responses to DNA damage. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2012. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/2142/29532.

Council of Science Editors:

Hsiao K. A histone H4 code regulates 53BP1-mediated responses to DNA damage. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2012. Available from: http://hdl.handle.net/2142/29532

26. Glauber Batista Gois. Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé.

Degree: 2016, Universidade Federal de Minas Gerais; UFMG

URL: http://hdl.handle.net/1843/BUOS-ARDHVX

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Impactos antropogênicos… (more)

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Impactos antropogênicos são uma ameaça crescente para a diversidade de peixes, especialmente em áreas em torno de grandes centros urbanos, e muitas ações efetivas de conservação dependem de identificação precisa das espécies. Considerando a utilidade do DNA Barcode como um sistema global de identificação e descoberta de espécies, este estudo tem como objetivo caracterizar molecularmente algumas espécies de peixes ornamentais e depositar sequências parciais do gene COI em uma biblioteca de referência. Seguindo essa metodologia, um fragmento da sub-unidade I da citocromo oxidase foi amplificado e sequenciado bidirecionalmente e a partir de 298 indivíduos. Uma análise de Neighbor-Joining revelou que esta abordagem pode discriminar inequivocamente todas as espécies pesquisadas. A maioria das espécies exibiu baixa distâncias genéticas intraespecíficas (1,53%), cerca de 9 vezes menor do que a distância entre as espécies dentro de um gênero. A biblioteca elaborada nesse estudo é um primeiro passo para conhecer melhor a diversidade molecular de peixes ornamentais, fornecendo uma base para futuros estudos sobre essa fauna - estendendo a capacidade de identificá-los em todas as fases da vida e até mesmo em restos ou fragmentos, fornecendo dados para uma melhor compreensão das interações entre as espécies, gerando estimativas sobre a composição de espécies e riqueza em um ecossistema, provendo ferramentas de autenticação de bioprodutos e monitoramento exploração ilegal de espécies.

Anthropogenic impacts are a rising threat to the diversity of fish, especially in areas around urban centers, and many effective conservation actions depend on accurate identification of species. Considering the usefulness of DNA Barcode as a global system of identification and discovery of species, this study aims to molecularly characterize the species of ornamental fish and provide partial COI gene sequences in a reference library. Following this methodology, a fragment of the subunit I of cytochrome oxidase gene was amplified and sequenced bidirectionally from 298. A Neighbor-Joining analysis showed that this approach can clearly discriminate all the surveyed species. Most of the species showed low intraspecific genetic distances (1.53%), about 9-fold less than the distance between species within a genus. The library developed in this study is a first step to better understand the molecular diversity of ornamental fish, providing a basis for future studies on this fauna - extending the ability to identify them in all life stages and even remnants or fragments, providing data for a better understanding of the interactions between species, generating estimates of the species composition and richness in an ecosystem, providing bioproducts authentication tools and monitoring illegal exploitation of species.

Advisors/Committee Members: Denise Aparecida Andrade de Oliveira, Daniela Chemim de Melo, Kleber Campos Miranda Filho, Eduardo Geraldo Alves Coelho.

Subjects/Keywords: DNA mitocondrial; Citocromo oxidase subunidade 1; Biodiversidade; Peixe ornamental Identificação; DNA mitocondrial; Biodiversidade

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

APA (6^th Edition):

Gois, G. B. (2016). Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé. (Masters Thesis). Universidade Federal de Minas Gerais; UFMG. Retrieved from http://hdl.handle.net/1843/BUOS-ARDHVX

Chicago Manual of Style (16^th Edition):

Gois, Glauber Batista. “Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé.” 2016. Masters Thesis, Universidade Federal de Minas Gerais; UFMG. Accessed April 16, 2021. http://hdl.handle.net/1843/BUOS-ARDHVX.

MLA Handbook (7^th Edition):

Gois, Glauber Batista. “Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé.” 2016. Web. 16 Apr 2021.

Vancouver:

Gois GB. Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé. [Internet] [Masters thesis]. Universidade Federal de Minas Gerais; UFMG; 2016. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1843/BUOS-ARDHVX.

Council of Science Editors:

Gois GB. Utilização da técnica de DNA Barcode para a identificação de espécies de peixes de água doce comercializados nas regiões de Belo Horizonte e Muriaé. [Masters Thesis]. Universidade Federal de Minas Gerais; UFMG; 2016. Available from: http://hdl.handle.net/1843/BUOS-ARDHVX

27. Racine, Pierre-Jean. Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication.

Degree: Docteur es, Biochimie, biologie cellulaire et moléculaire, physiologie et nutrition, 2012, Université Montpellier I

URL: http://www.theses.fr/2012MON1T023

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Le VIH-1 est un rétrovirus dont le génome est constitué d'ARN (ARNg). La conversion de cet ARNg en ADN est réalisée lors de la rétrotranscription… (more)

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Le VIH-1 est un rétrovirus dont le génome est constitué d'ARN (ARNg). La conversion de cet ARNg en ADN est réalisée lors de la rétrotranscription (RTion). Elle permet de convertir l'ARNg simple brin en une molécule d'ADN double brin, qui sera ensuite intégrée dans le génome de la cellule hôte pour assurer la réplication du virus. La RTion est réalisée dans les premières heures de l'infection, dès l'entrée du virus. La protéine de nucléocapside (NC) participe activement à cette conversion. La NC est une petite protéine avec deux motifs en doigt à zinc (ZF1 et ZF2) qui avec sa partie basique N-term sont responsables de son activité chaperonne des acides nucléiques. L'équipe a récemment découvert un nouveau rôle de la NC en observant que la mutation des doigts de zinc ou de la région basique N-term déclenche prématurément la RTion avant le relargage des nouveaux virus, c'est à dire pendant les phases tardives de réplication du VIH. Nous parlons alors de "RTion tardive". Celle-ci génère des virus à forte teneur en ADN viral. Ces résultats originaux indiquent que la NC joue un rôle dans le contrôle spatio-temporel de la RTion au cours de la réplication du VIH. Mon projet de thèse a consisté à identifier les partenaires potentiels de la NC dans cette RT tardive et à élucider les mécanismes moléculaires mis en jeu. L'approche expérimentale principalement utilisée au cours de ma thèse, consiste à la production de particules VIH-1 (pNL4-3) et à l'analyse de leur contenu en acides nucléiques par PCR quantitative en temps réel. En mesurant l'effet de la présence et de l'absence de la protéine virale Vif sur le déclenchement de la RTion tardive dans des cellules produisant le VIH-1, nous avons démontré l'implication de Vif dans la régulation de la RTion tardive. Nous avons également montré que l'ARNg, et plus particulièrement sa région 5'UTR, est un partenaire essentiel de la NC et de Vif dans le contrôle du timing de la RTion tardive. Notre étude comparative avec un rétrovirus plus ancien et plus simple (pas de Vif) comme le Murine Leukemia Virus (MuLV), montre que cette propriété de la NC du VIH-1 à contrôler la RTion tardive n'est pas commune à tous les rétrovirus. Pour mieux comprendre le rôle de la NC au cours des phases tardives de la réplication du VIH-1, nous avons utilisé la technique de microscopie TIRF (Total Internal Reflection Fluorescence microscopy) en cellules vivantes. Cette technique de microscopie permet de visualiser les étapes d'assemblage, de bourgeonnement et de relargage des particules virales à la membrane plasmique de la cellule hôte. Bien que la NC n'influe pas sur la cinétique d'assemblage du virus, elle est en revanche fortement impliquée dans le contrôle du bourgeonnement et du relargage des particules VIH-1. Des expériences de trans-complémentation du VIH-1 mutant (délétion du ZF2) montrent que la NC contribue au recrutement des protéines cellulaires ESCRT (Endosomal Sorting Complex Required for Transport) aux sites d'assemblage viral, notamment via la voie Tsg101.

HIV-1 is a retrovirus whose…

Advisors/Committee Members: Mougel, Marylène (thesis director).

Subjects/Keywords: Hiv-1; Rétrotranscription; Nucléocapside; Adn; Arn; Assemblage; Hiv-1; Reverse transcription; Nuclécapsid; Dna; Rna; Assembly

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

APA (6^th Edition):

Racine, P. (2012). Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON1T023

Chicago Manual of Style (16^th Edition):

Racine, Pierre-Jean. “Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed April 16, 2021. http://www.theses.fr/2012MON1T023.

MLA Handbook (7^th Edition):

Racine, Pierre-Jean. “Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication.” 2012. Web. 16 Apr 2021.

Vancouver:

Racine P. Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Apr 16]. Available from: http://www.theses.fr/2012MON1T023.

Council of Science Editors:

Racine P. Etude du contrôle spatiotemporel de la rétrotranscription au cours des phases tardives de la réplication du VIH-1 : Study of the spatiotemporal control of the reverse transcription during the late phases of HIV-1 replication. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON1T023

Queens University

28. Gupta, Neeraj. DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice .

Degree: Pharmacology and Toxicology, 2011, Queens University

URL: http://hdl.handle.net/1974/6465

► 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen found in unburned tobacco and tobacco smoke. To exert its carcinogenic effect, NNK is metabolically activated to reactive… (more)

Subjects/Keywords: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone ; Oxidative DNA Damage ; Base Excision Repair

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

APA (6^th Edition):

Gupta, N. (2011). DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice . (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/6465

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):

Gupta, Neeraj. “DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice .” 2011. Thesis, Queens University. Accessed April 16, 2021. http://hdl.handle.net/1974/6465.

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

MLA Handbook (7^th Edition):

Gupta, Neeraj. “DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice .” 2011. Web. 16 Apr 2021.

Vancouver:

Gupta N. DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice . [Internet] [Thesis]. Queens University; 2011. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1974/6465.

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

Council of Science Editors:

Gupta N. DNA oxidation and base excision repair in lung and liver of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone treated mice . [Thesis]. Queens University; 2011. Available from: http://hdl.handle.net/1974/6465

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

University of Rochester

29. Silva, Jharon Nirav. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.

Degree: PhD, 2013, University of Rochester

URL: http://hdl.handle.net/1802/27273

► Cerebral blood flow (CBF) is dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. To test whether dysregulation of CBF might be… (more)

▼ Cerebral blood flow (CBF) is dysregulated in persons with human immunodeficiency virus 1 (HIV-1), for uncertain reasons. To test whether dysregulation of CBF might be due to virally-induced neuroinflammation, we used a well-defined animal model (GFAP-driven, doxycycline [Dox]-inducible HIV-1 Tat transgenic [Tat-tg] mice) of HIV-associated neuroinflammation. We first studied the response to brief hypercapnia in a model for acute HIV-induced neuroinflammation (Tat-tg mice treated with Dox for 3 weeks). In control animals, brief hypercapnia induced a brisk increase in cortical flow (20.8% above baseline) and vascular dilation, as measured by laser Doppler flowmetry and in vivo two-photon microscopy. These responses were significantly attenuated in mice that were acutely exposed to Tat (11.6% above baseline), but cortical microvascular morphology and capillary density were unaltered, suggesting that the acute, Tat-induced functional pathology was not secondary to vascular remodeling. To examine the mechanistic basis for the diminished cerebrovascular response to brief hypercapnia in mice acutely exposed to Tat, animals were treated with (i) gisadenafil, a phosphodiesterase 5 (PDE5) inhibitor and (ii) tetrahydrobiopterin (BH4). Gisadenafil largely restored the normal increase in cortical flow following hypercapnia in Tat-tg mice (17.5% above baseline), whereas BH4 had little effect. Gisadenafil also restored the dilation of small (<25μm) arterioles following hypercapnia (19.1% versus 20.6% diameter increase in control and Tat-tg + gisadenafil, respectively), although it failed to restore full dilation of larger (>25μm) vessels. Taken together, these data show that acute HIV-associated neuroinflammation can cause cerebrovascular pathology, through effects on cGMP metabolism and possibly PDE5. In follow-up experiments, we examined the effects of chronic intracranial Tat exposure, by studying Tat-tg animals that were exposed to Dox for 5-7 months. These studies revealed a significant reduction in capillary density relative to age-matched control mice. These findings suggest that HIV-associated neuroinflammation may cause two distinct forms of cerebrovascular pathology: (i) loss of normal cerebrovascular reactivity due to perturbation of normal vasodilation and cGMP-mediated signaling and (ii) a chronic remodeling of the cerebral vasculature that results in a reduction in cerebral capillary density.

Subjects/Keywords: Cerebrovascular; HIV; Tat; Phosphodiesterase

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

APA (6^th Edition):

Silva, J. N. (2013). Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/27273

Chicago Manual of Style (16^th Edition):

Silva, Jharon Nirav. “Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.” 2013. Doctoral Dissertation, University of Rochester. Accessed April 16, 2021. http://hdl.handle.net/1802/27273.

MLA Handbook (7^th Edition):

Silva, Jharon Nirav. “Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density.” 2013. Web. 16 Apr 2021.

Vancouver:

Silva JN. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. [Internet] [Doctoral dissertation]. University of Rochester; 2013. [cited 2021 Apr 16]. Available from: http://hdl.handle.net/1802/27273.

Council of Science Editors:

Silva JN. Modeling the Effect of HIV-1 Induced Neuroinflammation on the Cerebral Vasculature: Acute Intracranial Exposure to HIV-1 Tat Leads to Dysregulation of Cerebrovascular Reactivity, While Chronic Tat Exposure Results in Reduced Vascular Density. [Doctoral Dissertation]. University of Rochester; 2013. Available from: http://hdl.handle.net/1802/27273

University of Manchester

30. Lawless, Michael. An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure.

Degree: 2014, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:244109

► Heart failure is the leading cause of morbidity and mortality in the world. It is an incurable disease and most treatment strategies aim to treat… (more)

▼ Heart failure is the leading cause of morbidity and mortality in the world. It is an incurable disease and most treatment strategies aim to treat the symptoms or slow the progression of the condition. Cardiac contractility is governed by calcium homeostasis within cardiac myocytes and is modulated by the sympathetic nervous system. Both mechanisms are detrimentally altered in heart failure. An important group of enzymes, phosphodiesterases, are fundamental to the sympathetic (beta-adrenergic) modulation of calcium cycling in cardiac myocytes. The selective inhibition of phosphodiesterase 5 (PDE5) has recently been considered as a potential therapy for heart failure; having beneficial effects in human and animal models of the disease. The present study employs a large animal model of tachypacing induced heart failure to test the effect of PDE5 inhibition on myocyte and whole heart contractility and beta-adrenergic function, to assess the molecular mechanisms by which PDE5 inhibition is beneficial to the failing myocardium.In initial experiments the PDE5 inhibitor sildenafil was applied acutely to voltage clamped ventricular myocytes from uninstrumented sheep. PDE5 inhibition reduced baseline L-type calcium current and systolic calcium transient amplitude, suggesting it is negatively inotropic. Furthermore, the positive inotropic effects of beta-adrenergic stimulation were somewhat reversed by acute PDE5 inhibition. Interestingly, such negative inotropic effects of acute PDE5 inhibition were not observed in failing ventricular myocytes, which have dysfunctional calcium homeostasis and beta-adrenergic reserve. When delivered chronically over 3 weeks to tachypaced animals, PDE5 inhibition restored and augmented the systolic calcium transient and beta-adrenergic responsiveness at both the whole heart and myocyte level. These effects were associated with changes to the expression and phosphorylation status of the proteins that control calcium homeostasis in left ventricular tissue. In vivo, PDE5 inhibition prolonged longevity and reduced the onset of clinical signs of heart failure in sheep, as well as arresting cardiac dilatation and wall thinning. Chronic PDE5 inhibition however had no effect on cardiac contractility or heart failure induced changes in cardiac electrophysiology.This study presents a novel mechanism by which PDE5 inhibition may be beneficial in a large animal model of heart failure by restoring calcium homeostasis and beta-adrenergic responsiveness. This study may have important implications for the management of heart failure in clinical practice. Advisors/Committee Members: EISNER, DAVID DA, Eisner, David, Trafford, Andrew.

Subjects/Keywords: heart failure; phosphodiesterase 5; calcium

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

APA (6^th Edition):

Lawless, M. (2014). An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:244109

Chicago Manual of Style (16^th Edition):

Lawless, Michael. “An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure.” 2014. Doctoral Dissertation, University of Manchester. Accessed April 16, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:244109.

MLA Handbook (7^th Edition):

Lawless, Michael. “An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure.” 2014. Web. 16 Apr 2021.

Vancouver:

Lawless M. An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Apr 16]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:244109.

Council of Science Editors:

Lawless M. An integrative assessment of phosphodiesterase 5 inhibition on cardiac function in heart failure. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:244109

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