subject:(QR Microbiology)

University of Huddersfield

1. Albarbar, Balid. The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate.

Degree: 2016, University of Huddersfield

URL: http://eprints.hud.ac.uk/id/eprint/31226/1/__nas01_librhome_librsh3_Desktop_FINAL%20THESIS.pdf

► LTβR and HVEM are non-death domain-containing TNFRs that can induce cell death via possible recruitment of TNFR-associated factors (TRAF), thus may share similarities to other… (more)

▼ LTβR and HVEM are non-death domain-containing TNFRs that can induce cell death via possible recruitment of TNFR-associated factors (TRAF), thus may share similarities to other TNFR members (e.g. CD40). This thesis aimed to investigate the effects of soluble LT agonists on a panel of carcinoma cells of colorectal (CRC) and bladder (UCC) origins and to compare the ability of these agonists to induce cell death against membrane-bound LIGHT (mLIGHT), and to unravel for the first time the cell signalling pathways responsible for mLIGHT-mediated cell death. Due to the complexity of some of the approaches used, a significant part of the experimental work involved optimisations involving not only soluble LT agonists, cytokines, specific pharmacological inhibitors but mainly optimisation for the first time of a co-culture system for the delivery of the mLIGHT signal to epithelial cells (involved co-culture of target cells with growth-arrested third-party L cells expressing surface mLIGHT). Several assays were also optimised for detection of cell viability, cell death (based on protease release, caspase activation and DNA fragmentation) and for detection of pro-inflammatory cytokine secretion. Moreover, immunoblotting techniques were optimised and utilised for detection of proteins associated with intracellular LTβR and HVEM-signalling. Transfection experiments using specific small interfering RNAs (siRNAs) were also employed to knockdown the expression of LTβR and HVEM proteins in CRC and UCC cells. This project revealed for the first time that normal human urothelial cells (NHU), CRC and UCC cells express LTβR and HVEM, and that the activation of LTβR and HVEM by mLIGHT, in the absence of IFN-γ, is pro-apoptotic in carcinoma cells, whereas mLIGHT appeared to be cyto-protective in NHU cells. By contrast, soluble LT agonists were weakly pro-apoptotic and required IFN-γ to kill HT29 cells, yet this combination did not kill other, well-characterised carcinoma cell lines, in particular HCT116 and EJ cells. Moreover, mLIGHT caused some DNA fragmentation in HCT116, yet little DNA fragmentation was detected in HT29 and EJ cells. It was also found that mLIGHT caused IL-8 and GM-CSF secretion. mLIGHT triggered TRAF1 and TRAF3 induction and caused little detectable differences in phospho-ERK, -JNK and -p38 expression in CRC and UCC cells. Functional inhibition experiments showed that blockade of MEK/ERK abrogated death in all cell lines tested, and JNK inhibition attenuated death in HCT116 and EJ (but not HT29 cells) and p38 inhibition significantly attenuated, but not fully, mLIGHT-mediated cell death in CRC and UCC cells. Moreover, an NF-κB inhibitor partially reduced mLIGHT-mediated death in CRC cells and potentiated it in UCC cells, whereas, inhibition of AP-1 partially blocked mLIGHT-mediated death in HCT116 and EJ cells. By contrast, AP-1 blockade did not cause any statistically significant effect in mLIGHT-mediated death in HT29 cells. Moreover, mLIGHT-mediated death is ROS dependent in CRC and UCC cells as the…

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Albarbar, B. (2016). The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate. (Doctoral Dissertation). University of Huddersfield. Retrieved from http://eprints.hud.ac.uk/id/eprint/31226/1/__nas01_librhome_librsh3_Desktop_FINAL%20THESIS.pdf

Chicago Manual of Style (16^th Edition):

Albarbar, Balid. “The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate.” 2016. Doctoral Dissertation, University of Huddersfield. Accessed February 27, 2021. http://eprints.hud.ac.uk/id/eprint/31226/1/__nas01_librhome_librsh3_Desktop_FINAL%20THESIS.pdf.

MLA Handbook (7^th Edition):

Albarbar, Balid. “The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate.” 2016. Web. 27 Feb 2021.

Vancouver:

Albarbar B. The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate. [Internet] [Doctoral dissertation]. University of Huddersfield; 2016. [cited 2021 Feb 27]. Available from: http://eprints.hud.ac.uk/id/eprint/31226/1/__nas01_librhome_librsh3_Desktop_FINAL%20THESIS.pdf.

Council of Science Editors:

Albarbar B. The role of lymphotoxin ligand-receptor interactions in regulating epithelial cell fate. [Doctoral Dissertation]. University of Huddersfield; 2016. Available from: http://eprints.hud.ac.uk/id/eprint/31226/1/__nas01_librhome_librsh3_Desktop_FINAL%20THESIS.pdf

University of Huddersfield

2. Moxon, Samuel Robert. Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds.

Degree: 2016, University of Huddersfield

URL: http://eprints.hud.ac.uk/id/eprint/32634/1/FINAL%20THESIS%20-%20MOXON.pdf

► As global life expectancy increases, so does the demand for new technologies to address healthcare issues associated with disease and degradation of biological tissues and… (more)

▼ As global life expectancy increases, so does the demand for new technologies to address healthcare issues associated with disease and degradation of biological tissues and organs. Implantation is still a heavily relied upon method but patient demand is far greater than donor availability. Tissue engineering continues to show promise as a potential alternative to the reliance on donors and is fundamentally based on the concept of using a patient’s own cells to create new, healthy tissue. Strategies often include incorporation of cells into 3D culture scaffolds as a means of replicating in vivo culture environments in vitro, thus stimulating expression of more native cellular phenotypes. Biopolymer hydrogels are popular tools for this approach due to lack of cytotoxicity, high porosity and a capacity to both introduce chemical cues and tune mechanical properties. Research, however, often focuses on culturing a single cell type and scaffolds often only exhibit a single mechanical property. Additionally, there is difficulty in delivering different chemical cues to a single encapsulated population due to limitations in controlling diffusion of small molecules through hydrogel matrices. This places limitations on the capacity to fabricate scaffolds for repair of complex layered structures comprised of multiple matrix components and cell types. The work presented in this thesis focuses on development of biopolymer hydrogel culture systems for providing cells with multiple chemical and mechanical cues. This could provide a platform for creating scaffolds for regeneration of more complex, layered structures such as articular cartilage and osteochondral tissue. Chapter 4 presents a study into using pulsed sonication to tune mechanical properties of hydrogel scaffolds of gellan gum (gellan). By applying different amplitudes of sonication, molecular weight was successfully tuned as evidenced by changes in intrinsic viscosity. This resulted in changes in both the dynamic viscosity of gellan solutions and the matrix stiffness and elasticity of gellan hydrogels. The impact on tuning mechanical properties of gellan hydrogels on cell behaviour was investigated using MC3T3 mouse pre-osteoblasts. A reduction in matrix stiffness via sonication coincided with a drop in expression of a key osteogenic marker, namely alkaline phosphatase. This demonstrated how tuning mechanical properties of gellan scaffolds with sonication could potentially be used to influence phenotype expression of many cell types with a possibility to influence cell differentiation. Chapters 5 and 6 build on this concept of manipulating mechanical properties to influence cell behaviour in vitro. Fluid gels are presented as a material for supporting deposition of biopolymer solutions for additive layer manufacturing of tissue culture scaffolds. The aim was to use this system to fabricate scaffolds exhibiting multiple mechanical properties and multiple cell types. Chapter 5 presents development of the method with investigation into how fluid gel mechanical…

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Moxon, S. R. (2016). Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds. (Doctoral Dissertation). University of Huddersfield. Retrieved from http://eprints.hud.ac.uk/id/eprint/32634/1/FINAL%20THESIS%20-%20MOXON.pdf

Chicago Manual of Style (16^th Edition):

Moxon, Samuel Robert. “Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds.” 2016. Doctoral Dissertation, University of Huddersfield. Accessed February 27, 2021. http://eprints.hud.ac.uk/id/eprint/32634/1/FINAL%20THESIS%20-%20MOXON.pdf.

MLA Handbook (7^th Edition):

Moxon, Samuel Robert. “Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds.” 2016. Web. 27 Feb 2021.

Vancouver:

Moxon SR. Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds. [Internet] [Doctoral dissertation]. University of Huddersfield; 2016. [cited 2021 Feb 27]. Available from: http://eprints.hud.ac.uk/id/eprint/32634/1/FINAL%20THESIS%20-%20MOXON.pdf.

Council of Science Editors:

Moxon SR. Development of Biopolymer Hydrogels as Complex Tissue Engineering Scaffolds. [Doctoral Dissertation]. University of Huddersfield; 2016. Available from: http://eprints.hud.ac.uk/id/eprint/32634/1/FINAL%20THESIS%20-%20MOXON.pdf

3. Wong, Soon Chuan. Development of a flicking system for producing 3-dimensional cells in microbeads.

Degree: Faculty of Electrical and Electronic Engineering, 2017, Universiti Tun Hussein Onn Malaysia

URL: http://eprints.uthm.edu.my/id/eprint/10239/

► Culturing cells on planar compliant substrates produces low yield of microtissues. A variety of microtechnologies was introduced and developed to encapsulate cells for producing microtissues.… (more)

▼ Culturing cells on planar compliant substrates produces low yield of microtissues. A variety of microtechnologies was introduced and developed to encapsulate cells for producing microtissues. However, the size control of the microcapsules is challenging to the current technologies for cells encapsulation. In this research, we proposed a simple yet efficient technique to encapsulate cells leading to the growth of microtissues. The technique involved with the development of a flicking system which can be applied to encapsulate cells in calcium alginate microbeads at different flow rates and flicking speed. The microbeads size increased with the flow rate but decreased with the flicking speed. Flicking speed of 80 rpm and flow rate of 4 μl/min was chosen to use in the cells encapsulation. The cells encapsulated in the microbeads at cell density of 31.9 × 106 cells/ml (HaCaT) and 94.2 × 106 cells/ml (ORL-48) were cultured and observed for proliferation over a period of time. The microbeads had a smooth surface with spongy and porous surface texture in FE-SEM imaging. In nucleus (DAPI) staining, the encapsulated HaCaT and ORL-48 cells in microbeads grew from scatter individual cells to form cells aggregate and then microtissues. In live and dead cells stainings, majority (≈99 %) of the microtissues cultured in the calcium alginate microbeads were stained in green which indicated the cells were alive. Alginate lyase was used to dissolve the alginate shells in which, the intact microtissues was released. The microtissues obtained were characterised by a rough and uneven surface could be due to the extracellular matrix proteins adjoining the cells. The cells of microtissues were viable and able to proliferate and spread into 2D monolayer in replating experiment. The flicking system has produced microbeads with controllable size and allows the growth of microtissues. HaCaT and ORL-48 cells encapsulated in calcium alginate microbeads can integrate into microtissues after two weeks of culture.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Wong, S. C. (2017). Development of a flicking system for producing 3-dimensional cells in microbeads. (Masters Thesis). Universiti Tun Hussein Onn Malaysia. Retrieved from http://eprints.uthm.edu.my/id/eprint/10239/

Chicago Manual of Style (16^th Edition):

Wong, Soon Chuan. “Development of a flicking system for producing 3-dimensional cells in microbeads.” 2017. Masters Thesis, Universiti Tun Hussein Onn Malaysia. Accessed February 27, 2021. http://eprints.uthm.edu.my/id/eprint/10239/.

MLA Handbook (7^th Edition):

Wong, Soon Chuan. “Development of a flicking system for producing 3-dimensional cells in microbeads.” 2017. Web. 27 Feb 2021.

Vancouver:

Wong SC. Development of a flicking system for producing 3-dimensional cells in microbeads. [Internet] [Masters thesis]. Universiti Tun Hussein Onn Malaysia; 2017. [cited 2021 Feb 27]. Available from: http://eprints.uthm.edu.my/id/eprint/10239/.

Council of Science Editors:

Wong SC. Development of a flicking system for producing 3-dimensional cells in microbeads. [Masters Thesis]. Universiti Tun Hussein Onn Malaysia; 2017. Available from: http://eprints.uthm.edu.my/id/eprint/10239/

4. Sanusi, Shuaibu Babaji. Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia.

Degree: phd, Faculty of Applied Science and Technology, 2018, Universiti Tun Hussein Onn Malaysia

URL: http://eprints.uthm.edu.my/id/eprint/12175/

► Tuberculosis (TB) remains an escalating health crisis globally which prompts new approaches to find more effective therapeutic strategies. Medicinal plants of Malaysia have a significant… (more)

▼ Tuberculosis (TB) remains an escalating health crisis globally which prompts new approaches to find more effective therapeutic strategies. Medicinal plants of Malaysia have a significant role to play in being able to provide new therapeutic remedies. The local people of Kampung Peta (Jakun tribe), Endau Rompin claimed that local preparations of some plants are used to treat symptoms of tuberculosis. There is a need to validate the claim by tradition healers scientifically. The aim of this research is to search for anti-TB from plants of Taman Negara Johor Endau-Rompin, exploiting the traditional medical practices of the Jakun people. Aqueous and organic extracts of these plant species were screened for their antimycobacterial activity using agar disk diffusion assay, Tetrazolium Microplate Assay and agar plate assay against Mycobacterium smegmatis. The effect of the extract on mycobacterial cell at the cellular level was investigated upon treatment with the crude extracts via time-kill analysis, leakage of compound absorbing at 280nm, and field emission-scanning electron microscopy (FE-SEM). The findings revealed that methanol extract of Nepenthes ampularia displayed the largest zone of inhibition (DIZ=18.67 ± 0.58 mm). Ethyl acetate extract of Musa gracilis and hexane extract of N. ampularia exhibited the lowest minimum inhibitory concentration (MIC=0.39 mg/mL). Hexane extract of N. ampularia showed the lowest minimum bactericidal concentration (MBC= 1.56 mg/mL). At 3-fold of MIC, hexane extract of N. ampularia, ethyl acetate extract of M. gracilis and ethyl acetate extract of N. ampularia killed the entire bacterial cell within 8 h of exposure by causing the cell lysis. The GC-MS analysis revealed the presence of phytoconstituents that might contribute to the antimycobacterial effect. The study scientifically justified the use of the selected medicinal plant species by Jakun people. Further studies on N. ampularia and M. gracilis could lead to the development of new anti-TB drugs

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Sanusi, S. B. (2018). Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia. (Doctoral Dissertation). Universiti Tun Hussein Onn Malaysia. Retrieved from http://eprints.uthm.edu.my/id/eprint/12175/

Chicago Manual of Style (16^th Edition):

Sanusi, Shuaibu Babaji. “Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia.” 2018. Doctoral Dissertation, Universiti Tun Hussein Onn Malaysia. Accessed February 27, 2021. http://eprints.uthm.edu.my/id/eprint/12175/.

MLA Handbook (7^th Edition):

Sanusi, Shuaibu Babaji. “Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia.” 2018. Web. 27 Feb 2021.

Vancouver:

Sanusi SB. Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia. [Internet] [Doctoral dissertation]. Universiti Tun Hussein Onn Malaysia; 2018. [cited 2021 Feb 27]. Available from: http://eprints.uthm.edu.my/id/eprint/12175/.

Council of Science Editors:

Sanusi SB. Evaluation of anti-tuberculosis potentials of selected medicinal plants in Endau Rompin, Johor, Malaysia. [Doctoral Dissertation]. Universiti Tun Hussein Onn Malaysia; 2018. Available from: http://eprints.uthm.edu.my/id/eprint/12175/

5. Abdul Aziz, Muhamad Amiril Ashraf. Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia.

Degree: mphil, Faculty of Applied Science and Technology, 2018, Universiti Tun Hussein Onn Malaysia

URL: http://eprints.uthm.edu.my/id/eprint/12424/

► Johor is undergoing rapid socioeconomic development; some forms of prioritization of conservation area are needed as the best resemblance of original biodiversity. Through effective management,… (more)

▼ Johor is undergoing rapid socioeconomic development; some forms of prioritization of conservation area are needed as the best resemblance of original biodiversity. Through effective management, it would assist the state for a better conservation practice. The purpose of this research is to provide a baseline data of odonates in Johor to facilitate prioritization of conservation areas as well as in planning, managing and sustainable usage of biodiversity. The objectives of this research are to determine the diversity and species composition of odonates in selected sites in Johor, to map distribution pattern based on faunistic and ecological aspects and to identify identify prioritize conservation areas and potential sites for odonate tourism using priority grid analysis based on specific criteria. Samplings were carried out from November 2016 to October 2017 in nine selected sites in Johor. Adult odonates were collected using aerial net in each of the 21 stations located at equidistant of 50 m along a one km transect for a total of 648 man-hours. The species distribution map of odonate was determined using both direct and indirect approaches in visualizing the distribution patterns. Total of 2,222 individuals of 84 species from 13 families and 58 genera were recorded. From all the nine sites, Libellulidae was the most well-represented family in terms of species richness (44%) and abundance (59%). Shannon Diversity Index (H’), and Species Evenness Index (E’) were highest in Taman Negara Johor Endau-Rompin (H’= 3.16; E’= 0.73) and lowest in Hutan Lipur Soga Perdana (H’= 2.44; E’= 0.50). The site with highest priority was Hutan Lipur Sungai Bantang with a score value of 62 while the lowest priority was recorded in Hutan Lipur Gunung Pulai with a score value of 23. Similarly, site with the highest potential towards odonate tourism was Hutan Lipur Sungai Bantang with score value of 99 and Hutan Lipur Gunung Pulai being the lowest with score value of 55.This study indicated the usefulness of species distribution mapping as a tool to prioritize conservation areas. In addition, this study reveals the potential of odonates as product for entomotourism in Johor.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Abdul Aziz, M. A. A. (2018). Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia. (Masters Thesis). Universiti Tun Hussein Onn Malaysia. Retrieved from http://eprints.uthm.edu.my/id/eprint/12424/

Chicago Manual of Style (16^th Edition):

Abdul Aziz, Muhamad Amiril Ashraf. “Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia.” 2018. Masters Thesis, Universiti Tun Hussein Onn Malaysia. Accessed February 27, 2021. http://eprints.uthm.edu.my/id/eprint/12424/.

MLA Handbook (7^th Edition):

Abdul Aziz, Muhamad Amiril Ashraf. “Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia.” 2018. Web. 27 Feb 2021.

Vancouver:

Abdul Aziz MAA. Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia. [Internet] [Masters thesis]. Universiti Tun Hussein Onn Malaysia; 2018. [cited 2021 Feb 27]. Available from: http://eprints.uthm.edu.my/id/eprint/12424/.

Council of Science Editors:

Abdul Aziz MAA. Diversity, species composition and distribution of odonates (odonata) in Johor, Peninsular Malaysia. [Masters Thesis]. Universiti Tun Hussein Onn Malaysia; 2018. Available from: http://eprints.uthm.edu.my/id/eprint/12424/

6. Babaji Sanusi, Shuaibu. Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia.

Degree: Fakulti Sains, Teknologi dan Pembangunan Insan, 2014, Universiti Tun Hussein Onn Malaysia

URL: http://eprints.uthm.edu.my/id/eprint/7048/

► Tuberculosis (TB) remains one of the serious infectious diseases and has been characterized worldwide as an epidemic by World Health Organization (WHO). TB is still… (more)

▼ Tuberculosis (TB) remains one of the serious infectious diseases and has been characterized worldwide as an epidemic by World Health Organization (WHO). TB is still a public health problem in Malaysia. Baseline information on the disease situation is one of the prerequisites for the development of appropriate control measures. The cornerstone in proper management of TB patients is ensuring high awareness in communities about TB. Thus the current research is directed to investigate the epidemiology of TB, determined the level of public awareness of TB and some factors that are responsible for the emergence of TB. Retrospective method was used for collecting epidemiological data from the Batu Pahat chest clinic. All registered TB patients (total of 1213 patients) from 2008 to 2013 in Batu Pahat Chest Clinic were included in the study. On the other hand, the awareness study was carried out by the use of questionnaires. A two-stage cluster sampling method was used. 600 respondents were targeted which form the study sample. However, 498 questionnaires were returned. Descriptive data analysis was employed to describe the results in frequency and percentage distribution. It was discovered that there was an annually increase in TB incidence with pulmonary TB the most common infection in Batu Pahat. Almost all (92.7%) the TB cases were new. On the other hand, majority (87.0%) of respondents have heard about TB. Common symptoms identified by respondents were coughing for over 2 weeks (51.8%), hemoptysis (49.2%) and difficulty in breathing (50.2%). Smoking cigarette (74.3%), living with individual having chronic cough (71.5%) and HIV/AIDS (65.7%) were the common risk factors of TB identified by respondents. Most of the respondents (83.5%) were aware of the existence of TB drugs. However, the standard DOTs treatment duration of 6-9 months was identified by few (12.4%) respondents. This research provided information regarding TB status in Batu Pahat. The level of awareness among Batu Pahat general public about TB is fairly good. Meanwhile, more need to be done especially on diabetes as the risk factors of TB and treatment duration.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Babaji Sanusi, S. (2014). Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia. (Masters Thesis). Universiti Tun Hussein Onn Malaysia. Retrieved from http://eprints.uthm.edu.my/id/eprint/7048/

Chicago Manual of Style (16^th Edition):

Babaji Sanusi, Shuaibu. “Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia.” 2014. Masters Thesis, Universiti Tun Hussein Onn Malaysia. Accessed February 27, 2021. http://eprints.uthm.edu.my/id/eprint/7048/.

MLA Handbook (7^th Edition):

Babaji Sanusi, Shuaibu. “Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia.” 2014. Web. 27 Feb 2021.

Vancouver:

Babaji Sanusi S. Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia. [Internet] [Masters thesis]. Universiti Tun Hussein Onn Malaysia; 2014. [cited 2021 Feb 27]. Available from: http://eprints.uthm.edu.my/id/eprint/7048/.

Council of Science Editors:

Babaji Sanusi S. Epidemiological and awareness study of tuberculosis in Batu Pahat, Johor, Malaysia. [Masters Thesis]. Universiti Tun Hussein Onn Malaysia; 2014. Available from: http://eprints.uthm.edu.my/id/eprint/7048/

University of Glasgow

7. Magnussen, Helge Magnus. Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation.

Degree: PhD, 2020, University of Glasgow

URL: http://theses.gla.ac.uk/79033/

► The RING E3 ligase MDM2 is a primary negative regulator of the tumour suppressor protein p53. It blocks transcriptional activity and ubiquitinates p53, resulting in… (more)

▼ The RING E3 ligase MDM2 is a primary negative regulator of the tumour suppressor protein p53. It blocks transcriptional activity and ubiquitinates p53, resulting in proteasomal degradation. MDM2’s ligase activity depends on the dimerisation of its C-terminal RING domain with either itself or its homologue MDMX. The crystal structure of the MDM2-MDMX heterodimer RING domain in complex with E2-ubiquitin has recently been crystallised. In this complex, only the MDM2 RING domain binds an E2-ubiquitin complex whereas the MDMX RING domain does not. However, MDMX’s C-terminal tail supports ubiquitin binding. This complex assembly results in one MDM2-MDMX RING heterodimer bound to one E2-ubiquitin complex. Due to extensive aggregation of the MDM2 homodimer, no structural information of the homodimeric MDM2-E2-ubiquitin complex has been obtained to date. During the course of my studies, I developed a purification protocol to generate non-aggregated homodimeric MDM2 RING domain. Sufficient amounts of homogeneous protein could be isolated for crystallisation purposes and crystal structures of the MDM2 homodimer alone and in complex with E2-ubiquitin were obtained. The crystal structures show that the homodimer can simultaneously bind two molecules of E2ubiquitin. The E2-ubiquitin binding surface resembles the heterodimer but shows significant differences in the arrangement of helices adjacent to the RING domain. Upon DNA damage, p53 needs to be stabilised in order to trigger cell cycle arrest or apoptosis. This requires p53 to be uncoupled from MDM2-mediated downregulation and is achieved by a number of phosphorylation events on both proteins, which reduce the binding affinity between p53 and MDM2. However, mouse models suggest that additional mechanisms exist as p53 is stabilised even when the corresponding phosphorylation sites are mutated. In addition, p53 is reportedly stabilised by phosphorylation of MDM2 near the RING domain, a region that is sequentially far away from the p53-binding domain. So far, the molecular basis of this mechanism has been elusive. Here, I show that phosphorylation near the RING domain enhances MDM2’s catalytic activity. With my MDM2 purification protocol, homodimeric phospho-MDM2 was generated and the crystal structure in complex with E2-ubiquitin was obtained. The molecular basis and homodimer-specificity of this novel phosphoregulation will be discussed. The results presented here help to understand the molecular function of MDM2, particularly under DNA damage conditions, and might be beneficial in diagnostics. The purification protocol of homogeneous MDM2 RING domain will be helpful for further structure-based studies such as the design of an MDM2 RING domain inhibitor.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Magnussen, H. M. (2020). Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/79033/

Chicago Manual of Style (16^th Edition):

Magnussen, Helge Magnus. “Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation.” 2020. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/79033/.

MLA Handbook (7^th Edition):

Magnussen, Helge Magnus. “Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation.” 2020. Web. 27 Feb 2021.

Vancouver:

Magnussen HM. Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation. [Internet] [Doctoral dissertation]. University of Glasgow; 2020. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/79033/.

Council of Science Editors:

Magnussen HM. Structural characterisation of MDM2 RING domain: E2-ubiquitin binding and activation by phosphorylation. [Doctoral Dissertation]. University of Glasgow; 2020. Available from: http://theses.gla.ac.uk/79033/

University of Glasgow

8. Lacombe, Alice. Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components.

Degree: PhD, 2020, University of Glasgow

URL: http://theses.gla.ac.uk/81531/

► Apicomplexan parasites cause diseases such as malaria and toxoplasmosis. These parasites are obligate intracellular pathogen and divergent organisms whose cellular machineries often composed of unique… (more)

▼ Apicomplexan parasites cause diseases such as malaria and toxoplasmosis. These parasites are obligate intracellular pathogen and divergent organisms whose cellular machineries often composed of unique structures of functions compared to model organisms. Studying fundamental mitochondrial biology in these organisms means defining the ancestral core of eukaryotic pathways while simultaneously identifying organism specific traits, that may also inspire drug discovery. Organellar translation has been a focus for the latter in recent years. Due to extreme gene transfer to the nuclear genome, the apicomplexan mitochondrial genome encodes only three proteins: COXI, COXIII and COB, and a series of indirect evidence suggest active mitochondrial translation of these proteins. Evidence also point to several divergent features in this pathway compared to model organism, primarily the reliance on the import of the full set of tRNAs from the cytosol, and the unusual ribosome composition. Progress has been hampered by the lack of functional assays to detect apicomplexan mitochondrial translation, a shortage of knowledge of proteins involved in this process and the incapacity to detect mitoribosomes. We investigate the molecular detail of translation in apicomplexan organisms using Toxoplasma gondii as a model. tRNA affinity pull down identified 7 candidate proteins with potential role in mitochondrial tRNA import. Using a bioinformatics screen based on mRNA expression patterns, 279 candidate mitochondrial housekeeping components were identified in Toxoplasma. 11 were validated, including the mitoribosomal small subunit protein 35 (TgmS35). The small subunit of the mitoribosome was detected for the first time in apicomplexans through TgmS35 triple HA tagging. A new analytical pipeline detected defects in mitochondrial translation upon TgmS35 depletion, while other mitochondrial functions remain unaffected. Our findings provide further support for the divergent nature of apicomplexan mitochondrial translation and lay a foundation for the study of apicomplexan mitochondrial translation.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Lacombe, A. (2020). Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/81531/

Chicago Manual of Style (16^th Edition):

Lacombe, Alice. “Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components.” 2020. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/81531/.

MLA Handbook (7^th Edition):

Lacombe, Alice. “Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components.” 2020. Web. 27 Feb 2021.

Vancouver:

Lacombe A. Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components. [Internet] [Doctoral dissertation]. University of Glasgow; 2020. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/81531/.

Council of Science Editors:

Lacombe A. Mitochondrial translation in Toxoplasma gondii: Establishing tools, and characterizing essential mitoribosomal components. [Doctoral Dissertation]. University of Glasgow; 2020. Available from: http://theses.gla.ac.uk/81531/

University of Glasgow

9. Pandey, Shashank. Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains.

Degree: 2020, University of Glasgow

URL: http://theses.gla.ac.uk/81464/

► This thesis evaluates two strains of Escherichia coli MG1655 and MDS42 for their motility in different nutrient conditions in M9 minimal medium in 2 parts.… (more)

▼ This thesis evaluates two strains of Escherichia coli MG1655 and MDS42 for their motility in different nutrient conditions in M9 minimal medium in 2 parts. It evaluates the effect of genome deletion in the motility and also observes the heterogeneity despite sharing the same genetically encoded machinery. The first part investigates Escherichia coli strains’ motility in 5 different medium compositions and the second part explores the chemotactic response of MG1655 to the linear gradients of different concentrations of Glucose using a single-layer membrane-based microfluidic device. In Part 1, we study the motility of MG1655 and MDS42 in different concentrations of glucose and casamino acids in M9 minimal medium. The motility experiments conducted as a part of this study observed the average cell velocities in the range of 2.9 ± 0.5 μm/s, which are significantly less than the values recorded in literature, for the strain MG1655. The lowest motility occurs in the medium (without casamino acids) with 0M glucose, followed by 10mM Glucose and then 10μM glucose concentration. The same trend is visible in the case of both the strains MG1655 and MDS42. The presence of casamino acids did not significantly affect the motility of MG1655 in the presence or absence of Glucose. Whereas, in the case of MDS42, the casamino acids lower the motility in the presence of Glucose but tend to have no significant effect in the absence of Glucose. The two strains, however, showed no significant difference in average velocity under the same medium conditions. In Part 2, we record and evaluate the chemotaxis of the MG1655 strain, using a single-layer membrane-based microfluidic device. The device generates a linear gradient of 10μM and 10mM glucose, to observe the chemotaxis of the MG1655 strain. The average of mean velocities for the 10μM gradient was higher than those observed in the 10mM gradient, but the difference was not significant. The higher fraction of cells (~67%) under the 10mM gradient showed almost a straight-line trajectory, unlike the cells under 10μM gradient. The cells that followed a nearly straight line path did all the more so in the case of the 10mM glucose gradient.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Pandey, S. (2020). Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains. (Thesis). University of Glasgow. Retrieved from http://theses.gla.ac.uk/81464/

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):

Pandey, Shashank. “Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains.” 2020. Thesis, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/81464/.

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

MLA Handbook (7^th Edition):

Pandey, Shashank. “Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains.” 2020. Web. 27 Feb 2021.

Vancouver:

Pandey S. Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains. [Internet] [Thesis]. University of Glasgow; 2020. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/81464/.

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

Council of Science Editors:

Pandey S. Comparative study of the effect of nutrients on motility and chemotaxis of Escherichia coli strains. [Thesis]. University of Glasgow; 2020. Available from: http://theses.gla.ac.uk/81464/

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

University of Huddersfield

10. Ali, Antasar Mohamed. Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase.

Degree: 2016, University of Huddersfield

URL: http://eprints.hud.ac.uk/id/eprint/32663/1/FINAL%20THESIS%20-%20ALI.pdf

► Hexokinases are a family of enzymes that catalyse the phosphorylation of glucose by transferring the γ- phosphoryl group from adenosine triphosphate (ATP) to the sixth… (more)

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Ali, A. M. (2016). Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase. (Doctoral Dissertation). University of Huddersfield. Retrieved from http://eprints.hud.ac.uk/id/eprint/32663/1/FINAL%20THESIS%20-%20ALI.pdf

Chicago Manual of Style (16^th Edition):

Ali, Antasar Mohamed. “Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase.” 2016. Doctoral Dissertation, University of Huddersfield. Accessed February 27, 2021. http://eprints.hud.ac.uk/id/eprint/32663/1/FINAL%20THESIS%20-%20ALI.pdf.

MLA Handbook (7^th Edition):

Ali, Antasar Mohamed. “Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase.” 2016. Web. 27 Feb 2021.

Vancouver:

Ali AM. Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase. [Internet] [Doctoral dissertation]. University of Huddersfield; 2016. [cited 2021 Feb 27]. Available from: http://eprints.hud.ac.uk/id/eprint/32663/1/FINAL%20THESIS%20-%20ALI.pdf.

Council of Science Editors:

Ali AM. Biochemical Characterization of a Novel Mammalian Polyphosphate Dependent Glucokinase. [Doctoral Dissertation]. University of Huddersfield; 2016. Available from: http://eprints.hud.ac.uk/id/eprint/32663/1/FINAL%20THESIS%20-%20ALI.pdf

Cardiff University

11. Gamble, Michael. Stucture, function and folding of a novel subtilisin serine protease.

Degree: PhD, 2010, Cardiff University

URL: http://orca.cf.ac.uk/55015/

► ISPs constitute the major cellular proteolytic activity of many bacilli, yet their physiological role, mechanism of regulation and 3D structure were unknown. ISP from B.… (more)

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Gamble, M. (2010). Stucture, function and folding of a novel subtilisin serine protease. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/55015/

Chicago Manual of Style (16^th Edition):

Gamble, Michael. “Stucture, function and folding of a novel subtilisin serine protease.” 2010. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/55015/.

MLA Handbook (7^th Edition):

Gamble, Michael. “Stucture, function and folding of a novel subtilisin serine protease.” 2010. Web. 27 Feb 2021.

Vancouver:

Gamble M. Stucture, function and folding of a novel subtilisin serine protease. [Internet] [Doctoral dissertation]. Cardiff University; 2010. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/55015/.

Council of Science Editors:

Gamble M. Stucture, function and folding of a novel subtilisin serine protease. [Doctoral Dissertation]. Cardiff University; 2010. Available from: http://orca.cf.ac.uk/55015/

Cardiff University

12. Fyson, Sarah Jane. Tonic GABAa current in absence epilepsy.

Degree: PhD, 2010, Cardiff University

URL: http://orca.cf.ac.uk/55034/

► Typical absence seizures are characteristic of many idiopathic generalised epilepsies and the only seizure-type in childhood absence epilepsy. We know that absence seizures arise in… (more)

▼ Typical absence seizures are characteristic of many idiopathic generalised epilepsies and the only seizure-type in childhood absence epilepsy. We know that absence seizures arise in thalamocortical networks and that GABAergic agents exacerbate or induce absences. Furthermore, raised levels of GABA have been identified in the ventrobasal thalamus in an established genetic animal model (genetic absence epilepsy rats from Strasbourg GAERS), which was later suggested as a result of aberrant GABA uptake. I have shown that enhanced tonic GABAa current in TC neurons of the VB is a common phenomenon across genetic and pharmacological models of absence seizures. Furthermore, my data show that increased extrasynaptic GABAaR (cGABAaR) function in the VB is both sufficient and necessary to induce SWDs. This is supported by the fact that focal intrathalamic application of a selective agonist for eGABAARs, THIP, was sufficient to elicit SWDs in normal animals and that mice lacking cGABAaRs were resistant to absence seizure induction by y-butyrolactone. Moreover, I have presented data that directly implicate aberrant type-1 GABA transporters (GAT-1) in SWD generation in vivo, with GAT-1 knockout mice exhibiting spontaneous SWDs and focal thalamic administration of the GAT-1 blocker, N0711, inducing SWDs in normal rats a potential new model of absence epilepsy. In addition, my data indicate that activation of postsynaptic GABAbRs enhances tonic GABAA current, presumably via the Gl o protein coupled adenyl cyclase pathway, which was present under control conditions and occurred in several brain areas. This postsynaptic GABAb-cGABAaR link is further supported by the fact that GBL failed to induce SWDs in 5-subunit knockout mice. Thus, one of the cellular thalamic pathologies that characterises absence seizures is an astrocyte-specific aberrant GAT-1 with the resulting elevated extracellular GABA level enhancing tonic GABAa current through two mechanisms: direct activation of high affinity eGABAARs and indirect increase in eGABAAR function due to activation of postsynaptic GABAbRs.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Fyson, S. J. (2010). Tonic GABAa current in absence epilepsy. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/55034/

Chicago Manual of Style (16^th Edition):

Fyson, Sarah Jane. “Tonic GABAa current in absence epilepsy.” 2010. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/55034/.

MLA Handbook (7^th Edition):

Fyson, Sarah Jane. “Tonic GABAa current in absence epilepsy.” 2010. Web. 27 Feb 2021.

Vancouver:

Fyson SJ. Tonic GABAa current in absence epilepsy. [Internet] [Doctoral dissertation]. Cardiff University; 2010. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/55034/.

Council of Science Editors:

Fyson SJ. Tonic GABAa current in absence epilepsy. [Doctoral Dissertation]. Cardiff University; 2010. Available from: http://orca.cf.ac.uk/55034/

Cardiff University

13. O'Connor, Simon. Modelling gap junction-coupled networks of olfactory bulb mitral cells.

Degree: PhD, 2010, Cardiff University

URL: http://orca.cf.ac.uk/55041/

► Summary of Thesis: The olfactory bulb forms the first level of input integration for olfactory receptor neurons that receive stimuli from odorant molecules in the… (more)

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

O'Connor, S. (2010). Modelling gap junction-coupled networks of olfactory bulb mitral cells. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/55041/

Chicago Manual of Style (16^th Edition):

O'Connor, Simon. “Modelling gap junction-coupled networks of olfactory bulb mitral cells.” 2010. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/55041/.

MLA Handbook (7^th Edition):

O'Connor, Simon. “Modelling gap junction-coupled networks of olfactory bulb mitral cells.” 2010. Web. 27 Feb 2021.

Vancouver:

O'Connor S. Modelling gap junction-coupled networks of olfactory bulb mitral cells. [Internet] [Doctoral dissertation]. Cardiff University; 2010. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/55041/.

Council of Science Editors:

O'Connor S. Modelling gap junction-coupled networks of olfactory bulb mitral cells. [Doctoral Dissertation]. Cardiff University; 2010. Available from: http://orca.cf.ac.uk/55041/

Cardiff University

14. Evans, James. Modulation of the human gut microbiome in order to promote host health and well-being.

Degree: PhD, 2014, Cardiff University

URL: http://orca.cf.ac.uk/60061/

► Background. Numerous studies into the effect of probiotic supplementation in the infirm have been carried out. However, research into the effect of long-term probiotic supplementation… (more)

▼ Background. Numerous studies into the effect of probiotic supplementation in the infirm have been carried out. However, research into the effect of long-term probiotic supplementation in healthy individuals is lacking. With this in mind the PROHEMI study, a randomized, double-blinded, multi-centre and long-term (6 months) probiotic feeding study in healthy males was designed and carried out. Through the use of varied culture dependent and independent techniques, the effects of long-term probiotic consumption were researched. In addition, a study into the effect of freezing faecal material on its bacterial composition was also carried out. Results. Through a community fingerprinting technique and next generation sequencing it was shown that the distal gut bacterial community is unaffected by probiotic supplementation. Functional screening of faecal material showed a reduction in bacteria expressing protease activity when probiotic supplementation began. In addition, bacteria expressing β-galactosidase and β-glucuronidase activity increased during probiotic supplementation. Metabonomic analysis showed no difference in metabolite profiles attributable to probiotic supplementation. However, differences between the gut bacterial community, metabonomic profiles, and bacteria expressing functions were observed between the two study centres. Freezing of faecal material at -20°C detrimentally affected its bacterial composition between 2 weeks and 3 month storage time-points. Significant reductions in the abundance of the Bacteroidetes phylum observed following 6 months of storage at -20°C. Conclusions. Long-term probiotic administration in healthy individuals did not seem to affect the distal gut bacterial community in these individuals and did not affect metabonomic profiles. However, some functions expressed by the resident distal gut bacterial community were significantly affected during probiotic supplementation. DNA extraction from faecal material should ideally be carried out from fresh samples. Failing this it is not recommended to store samples at -20°C for longer than 2 weeks prior to DNA extraction.

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Evans, J. (2014). Modulation of the human gut microbiome in order to promote host health and well-being. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/60061/

Chicago Manual of Style (16^th Edition):

Evans, James. “Modulation of the human gut microbiome in order to promote host health and well-being.” 2014. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/60061/.

MLA Handbook (7^th Edition):

Evans, James. “Modulation of the human gut microbiome in order to promote host health and well-being.” 2014. Web. 27 Feb 2021.

Vancouver:

Evans J. Modulation of the human gut microbiome in order to promote host health and well-being. [Internet] [Doctoral dissertation]. Cardiff University; 2014. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/60061/.

Council of Science Editors:

Evans J. Modulation of the human gut microbiome in order to promote host health and well-being. [Doctoral Dissertation]. Cardiff University; 2014. Available from: http://orca.cf.ac.uk/60061/

Cardiff University

15. Morris, Laura. Towards accessing the proteolytic potential of the gut microbiota.

Degree: PhD, 2014, Cardiff University

URL: http://orca.cf.ac.uk/71458/

► Introduction:-The human gut microbiota outnumbers our own human cells by 100-1 and is often considered an extension of our genome harboring fundamental functions of which… (more)

▼ Introduction:-The human gut microbiota outnumbers our own human cells by 100-1 and is often considered an extension of our genome harboring fundamental functions of which we are genetically incapable. However, it can also be a significant liability and has been implicated in numerous diseases, particularly; Inflammatory Bowel Disease (IBD). The efforts of this research entailed evaluating a specific molecular mechanism of the gut bacterial metagenome; proteolytic activity, collectively known as the Degradome due to their putative role as significant virulence factors in IBD. In order to access this degradome of the gut microbiota, firstly, novel functional metagenomic (FM) tools were developed with an aim of facilitating the isolation of proteases. Secondly, a comprehensive cohort study was conducted comparing faecal protease activity, 16S rRNA microbial community structure and the potential of the faecal degradome to act as virulence factors between a group of IBD patients and a group of healthy volunteers to begin to determine the role of microbial proteases in disease aetiology. Results:-The IBD cohort exhibited significantly higher protease activity than the healthy cohort. Inhibitor assays also showed that the IBD cohort contained different types of proteases to the healthy cohort with significantly higher levels of metalloprotease activity. 16S rRNA gene analysis of the microbial community also revealed a dysbiosis of the gut microbiota between the IBD cohort and the healthy cohort. Dysbiosis was also observed between the high protease producers and the low protease producers and protease activity in the IBD cohort was able to decrease trans epithelial resistance in an HT-29 cell line and increase cellular permeability. Functional metagenomics tools were also assessed for isolation of proteases from the gut microbiota. The ability of a protease deficient strain; Bacillus subtilis WB800N to express proteases was compared with E. coli to determine its usefulness as a host for FM screening for proteases. B. subtilis WB800N was able to express gelatinase E and neutral protease while E. coli was not suggesting B. subtilis WB800N was more suitable as a host. However, when the gut microbiota was screened for proteases using this host, none were isolated suggesting improvements still needed to be made. Conclusions: - Compositional alterations of the gut microbiota appear to be associated with high and low levels of protease activity. The IBD cohort had elevated activity and an expanded repertoire of faecal proteases which also appear to have the potential to act as a virulence factor by disrupting epithelial cell barrier integrity. Proteases remain elusive via FM screening; however this study has highlighted the areas that need improvement to optimize future screens for accessing the degradome of the gut microbiota.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Morris, L. (2014). Towards accessing the proteolytic potential of the gut microbiota. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/71458/

Chicago Manual of Style (16^th Edition):

Morris, Laura. “Towards accessing the proteolytic potential of the gut microbiota.” 2014. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/71458/.

MLA Handbook (7^th Edition):

Morris, Laura. “Towards accessing the proteolytic potential of the gut microbiota.” 2014. Web. 27 Feb 2021.

Vancouver:

Morris L. Towards accessing the proteolytic potential of the gut microbiota. [Internet] [Doctoral dissertation]. Cardiff University; 2014. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/71458/.

Council of Science Editors:

Morris L. Towards accessing the proteolytic potential of the gut microbiota. [Doctoral Dissertation]. Cardiff University; 2014. Available from: http://orca.cf.ac.uk/71458/

Cardiff University

16. Alsabah, Ayesha. The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation.

Degree: PhD, 2014, Cardiff University

URL: http://orca.cf.ac.uk/72203/

► WNT signalling is a major driving force in cartilage development, chondrocyte differentiation, and homeostasis. Due to its major role in cartilage homeostasis, deregulation of this… (more)

▼ WNT signalling is a major driving force in cartilage development, chondrocyte differentiation, and homeostasis. Due to its major role in cartilage homeostasis, deregulation of this pathway was suggested to be involved in the pathophysiology of osteoarthritis, which causes cartilage degeneration. Studies have identified mutations in inhibitors of WNT signalling in OA tissue in addition to up-regulation of related WNT components. However, these studies have focused on the end stage of the disease and have not factored in mechanical loading which is one of the main regulators of cartilage homeostasis. Results: Canonical WNT signalling was activated in response to both tensile and compressive loading. Furthermore, WNT signalling was observed to be differentially regulated in bovine cartilage explants in response to physiological (2.5MPa, 1Hz, 15 minutes) and degradative (7MPa, 1Hz, 15 minutes) compressive loading in a zone dependent manner as indicated by β-catenin nuclear translocation. Based on periods post-cessation of load, physiological and degradative loads have induced differential matrix gene expression. In addition, both loading regimes have shown differential regulation of WNT signalling components displaying more WNT signalling activation in degradative loading regime. DKK-1 and NFATC, WNT signalling components which have shown to have a role in cartilage homeostasis, have been chosen for functional analysis studies. Treatment of recombinant DKK-1 in combination with degradative load have shown that DKK-1 primarily inhibited canonical WNT signalling pathway, whereas treatment with NFAT inhibitor induced inhibition of both WNT signalling pathways. In addition, both treatments were observed to inhibit some of the load-induced matrix gene changes. Conclusions: WNT signalling is mechano-regulated in articular cartilage. The differential expression of WNT signalling components in response to different mechanical load regimes indicates a role for these components in maintaining cartilage homeostasis.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Alsabah, A. (2014). The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/72203/

Chicago Manual of Style (16^th Edition):

Alsabah, Ayesha. “The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation.” 2014. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/72203/.

MLA Handbook (7^th Edition):

Alsabah, Ayesha. “The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation.” 2014. Web. 27 Feb 2021.

Vancouver:

Alsabah A. The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation. [Internet] [Doctoral dissertation]. Cardiff University; 2014. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/72203/.

Council of Science Editors:

Alsabah A. The role of canonical and non-canonical WNT signalling pathways in load induced cartilage degradation. [Doctoral Dissertation]. Cardiff University; 2014. Available from: http://orca.cf.ac.uk/72203/

Cardiff University

17. Cleal, Kez. Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins.

Degree: PhD, 2015, Cardiff University

URL: http://orca.cf.ac.uk/87577/

► Progress in the biological sciences is leading to the characterization of a wide range of disease processes in molecular detail. However overriding or intervening in… (more)

▼ Progress in the biological sciences is leading to the characterization of a wide range of disease processes in molecular detail. However overriding or intervening in these processes in a controlled fashion remains a great challenge and many researchers are now looking beyond the use of individual small molecule inhibitors to the realm of macromolecules and nanoparticle complexes. For small molecules, the lack of cell-specific targeting often limits their reach and they are inherently limited in the scope of their interaction with cells. In contrast, biological macromolecules which comprise of peptide, protein or nucleic acid derived constructs can interface with cellular processes in a broader range of contexts with the potential to confer new paradigms in disease treatment. However, several challenges exist for utilizing macromolecules as therapies including compliance with the immune system and targeting to a site of interest which may be the cell surface or a site within the cell interior. To address these problems recent years have seen an explosion of interest in utilizing nanoparticles as drug delivery systems which exploit the principle that multiple functionalities can be grouped into a single entity to tackle distinct biological barriers. Whilst nanoparticles offer great hope for disease management, there is considerable difficulty in fabricating at the nanoscale and our understanding of the factors which influence nanoparticle cell uptake and processing remains limited. As such there is considerable scope for exploring novel methods for both assembling cargoes into nanoparticle complexes and quantifying their uptake and trafficking in cells. In this work, luminescent nanoparticles known as Quantum dots (QDs) were utilized as a model system for the delivery of peptide, protein and small molecule cargoes. Characterization of QDs in biological media (Chapter 3) revealed that these particles are sensitive to the adsorption of serum proteins to the particle surface in a process known as protein corona formation. This observation inspired an approach to exploit non-covalent association to assemble a hydrophobic small molecule (Chapter 4), and cationic peptide and protein (Chapter 5) cargoes into nanoparticle complexes. In line with recent reports, a recurrent finding from this work identifies the serum protein concentration as a critical factor in determining the performance of these non-covalent nanoparticle complexes in terms of their ability to bind to cells and withstand cargo dissociation. Currently, there are few methods which aim to quantifying intracellular particle trafficking at a single particle level. Here a novel computational method was developed (Chapter 6) based on single particle tracking microscopy to allow the study of individual particles as they undergo transit between cellular compartments. The method demonstrated high specificity and event detection scores using simulated data and the impact of this work relates to the potential to perform high throughput quantification of nanoparticle…

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Cleal, K. (2015). Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/87577/

Chicago Manual of Style (16^th Edition):

Cleal, Kez. “Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins.” 2015. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/87577/.

MLA Handbook (7^th Edition):

Cleal, Kez. “Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins.” 2015. Web. 27 Feb 2021.

Vancouver:

Cleal K. Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins. [Internet] [Doctoral dissertation]. Cardiff University; 2015. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/87577/.

Council of Science Editors:

Cleal K. Exploring the use of Quantum dots as quantitative model delivery agents for small molecules, peptides and proteins. [Doctoral Dissertation]. Cardiff University; 2015. Available from: http://orca.cf.ac.uk/87577/

18. Jones, Cerith. Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa.

Degree: PhD, 2014, Imperial College London

URL: http://orca.cf.ac.uk/89225/

► Pseudomonas aeruginosa is a versatile and prevalent opportunistic pathogen. It encodes a large arsenal of pathogenicity factors, and secrets a plethora of proteins using specialised… (more)

▼ Pseudomonas aeruginosa is a versatile and prevalent opportunistic pathogen. It encodes a large arsenal of pathogenicity factors, and secrets a plethora of proteins using specialised protein secretion systems. The type VI secretion system (T6SS) delivers proteins directly into neighbouring bacteria or eukaryotic cells using a mechanism homologous to the T4 bacteriophage tail spike. Three T6SS are encoded on the P. aeruginosa genome. The study of the H1-T6SS has been facilitated by the fact it can be activated by the manipulation of the RetS/Gac/Rsm regulatory cascade by deletion of retS. However, the precise signals required for activation of this cascade, resulting in H1-T6SS activation, are unknown. This work investigates the role of subinhibitory concentrations of antibiotics in activating the system, and shows that kanamycin is able to induce production of core H1-T6SS components. This activation requires a functional Gac/Rsm cascade, but it is not known if this is due to direct signalling via the cascade, or due to a dominant effect of RsmA repression. The H2-T6SS is characterized in this work. We highlight key differences between the H2-T6SS cluster in PAO1 and PA14, including the presence of additional core T6SS components and putative secreted effectors. A strain is generated in which expression of the PA14 H2-T6SS cluster can be activated and tightly controlled by arabinose inducible promoters. The activity of the promoters is confirmed by the H2-T6SS dependent secretion of Hcp2 specifically upon arabinose induction. We further consider two putative H2-T6SS secreted substrates, VgrG14 and Rhs14. Production of these proteins is observed following arabinose induction, but their secretion is not detected. The Rhs14 protein is characterised, and its possible role as a H2-T6SS dependent effector is discussed. Finally, the H2-T6SS system in PA14 is shown to inhibit the internalisation of P. aeruginosa PA14, in contrast to the previously published observations of the H2-T6SS promoting internalisation of PAO1.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Jones, C. (2014). Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa. (Doctoral Dissertation). Imperial College London. Retrieved from http://orca.cf.ac.uk/89225/

Chicago Manual of Style (16^th Edition):

Jones, Cerith. “Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa.” 2014. Doctoral Dissertation, Imperial College London. Accessed February 27, 2021. http://orca.cf.ac.uk/89225/.

MLA Handbook (7^th Edition):

Jones, Cerith. “Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa.” 2014. Web. 27 Feb 2021.

Vancouver:

Jones C. Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa. [Internet] [Doctoral dissertation]. Imperial College London; 2014. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/89225/.

Council of Science Editors:

Jones C. Activation and functional studies of the Type VI secretion systems in Pseudomonas aeruginosa. [Doctoral Dissertation]. Imperial College London; 2014. Available from: http://orca.cf.ac.uk/89225/

Cardiff University

19. Sanders, Rebecca. Precision in RNA molecular measurement.

Degree: PhD, 2016, Cardiff University

URL: http://orca.cf.ac.uk/91295/

► Measurement of gene expression profiles represents a snapshot of cellular metabolism or activity at the molecular scale. This involves measurement of messenger (m)RNA employing techniques… (more)

▼ Measurement of gene expression profiles represents a snapshot of cellular metabolism or activity at the molecular scale. This involves measurement of messenger (m)RNA employing techniques such as reverse transcription quantitative polymerase chain reaction (RT-qPCR). To truly assign biological significance to associated findings, researchers must consider the idiosyncrasies of this method and associated technical error, termed measurement uncertainty. Significant error can occur at sample source, RNA extraction, RT and qPCR levels. This thesis explores the steps which may introduce potential bias. It is hypothesised that error in mRNA measurement can be partitioned across different experimental stages. Within this thesis, RNA measurement from sample source to qPCR has been analysed at each stage to delineate variability contributions attributed to specific steps using synthetic and validated endogenous reference genes, single cell lines, 3D models and complex bone tissue. These data determined that total RNA yields remained consistent between treatment (2D cell mineralisation, 3D co-culture mechanical loading) and control groups (p > 0.06). Sample complexity was positively correlated with RNA extraction yield variability. Evaluation of different extraction methods demonstrated that total RNA yields differed between methods (p < 0.001). Assessing total RNA quantity and quality, different metrics (Bioanalyzer, Nanodrop and Qubit) generated different yield estimates (p < 0.05), although quality estimates from different metrics were found to be comparable. In addition, different cell batches (cultures of the same cells from different cryo vials) generated disparate total RNA yields (p < 0.02), with variable quality estimates, despite normalisation for cell count. RT-digital PCR analysis revealed quantification differences and detection sensitivity biases between different RT enzymes (p < 0.0001), suggesting cDNA prepared using different RT enzymes cannot be meaningfully compared. The ERCC synthetic targets were variable under the model conditions assessed and therefore not suitable as normalisers in these circumstances. This work provides a guide for the approaches necessary to reduce error, improve experimental design and minimise uncertainties.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Sanders, R. (2016). Precision in RNA molecular measurement. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/91295/

Chicago Manual of Style (16^th Edition):

Sanders, Rebecca. “Precision in RNA molecular measurement.” 2016. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/91295/.

MLA Handbook (7^th Edition):

Sanders, Rebecca. “Precision in RNA molecular measurement.” 2016. Web. 27 Feb 2021.

Vancouver:

Sanders R. Precision in RNA molecular measurement. [Internet] [Doctoral dissertation]. Cardiff University; 2016. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/91295/.

Council of Science Editors:

Sanders R. Precision in RNA molecular measurement. [Doctoral Dissertation]. Cardiff University; 2016. Available from: http://orca.cf.ac.uk/91295/

Cardiff University

20. Green, Angharad. Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain.

Degree: PhD, 2017, Cardiff University

URL: http://orca.cf.ac.uk/108193/

► Pseudomonas aeruginosa is a common industrial contaminant associated with costly recalls of home and personal care(HPC) products. Preservation systems are used to prevent bacterial contamination… (more)

▼ Pseudomonas aeruginosa is a common industrial contaminant associated with costly recalls of home and personal care(HPC) products. Preservation systems are used to prevent bacterial contamination and protect consumers, but little is known about the mechanisms of preservative resistance in P. aeruginosa. The aim of this research was to map genetic and metabolic pathways associated with preservative resistance and bacterial growth in HPC products. The genome of the industrial strain P. aeruginosa RW109 was sequenced, functionally annotated, and compared to other strains of the species. This revealed the first complete genome of a P. aeruginosa isolate from the HPC industry. Comparative analysis with 102 P. aeruginosa strains from various sources, showed industrial strains’ genomes to be significantly larger than clinical and environmental strains and RW109’s genome was the largest of the species (7.8 Mbp) and included two plasmids. Identification of differentially expressed genes by RNA-Seq (more informative than mini-Tn5-luxCDABE mutagenesis), revealed complex genetic networks utilised by RW109 when exposed to benzisothiazolone(BIT), phenoxyethanol (POE) and a laundry detergent formulation. Differential expression of five sets of genes was consistently observed in response to these industry relevant conditions - MexPQ-OpmE efflux pump, sialic acid transporter and isoprenoid biosynthesis (gnyRDBHAL) genes were frequently upregulated; whereas phnBA and pqsEDCBA genes encoding PQS production and quorum-sensing, respectively, were consistently down-regulated. Genome-scale metabolic network reconstruction of RW109, the first with a P. aeruginosa industrial strain, along with integration of transcriptomic data, predicted essential pathways for RW109’s preservative resistance (e.g. cell membrane phospholipid biosynthesis as a key pathway for POE resistance). This study highlights the utility of integrating genomic, transcriptomic and metabolic modelling approaches to uncover the basis of industrial bacterial resistance to preservative and product formulations. The ability to predict the metabolic basis of P. aeruginosa preservative resistance will inform the development of targeted industrial preservation systems, enhancing product safety and minimising future resistance development.

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Green, A. (2017). Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/108193/

Chicago Manual of Style (16^th Edition):

Green, Angharad. “Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain.” 2017. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/108193/.

MLA Handbook (7^th Edition):

Green, Angharad. “Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain.” 2017. Web. 27 Feb 2021.

Vancouver:

Green A. Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain. [Internet] [Doctoral dissertation]. Cardiff University; 2017. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/108193/.

Council of Science Editors:

Green A. Investigating the genetic basis of preservative resistance in an industrial Pseudomonas aeruginosa strain. [Doctoral Dissertation]. Cardiff University; 2017. Available from: http://orca.cf.ac.uk/108193/

Cardiff University

21. Leggett, Mark J. Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing.

Degree: PhD, 2010, Cardiff University

URL: http://orca.cf.ac.uk/54121/

► This study aimed to investigate the RBT outcome as a function of the bacterial inoculum during adaptation to degrade the HAs dichloroacetic acid (DCA), trichloroacetic… (more)

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Leggett, M. J. (2010). Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/54121/

Chicago Manual of Style (16^th Edition):

Leggett, Mark J. “Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing.” 2010. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/54121/.

MLA Handbook (7^th Edition):

Leggett, Mark J. “Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing.” 2010. Web. 27 Feb 2021.

Vancouver:

Leggett MJ. Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing. [Internet] [Doctoral dissertation]. Cardiff University; 2010. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/54121/.

Council of Science Editors:

Leggett MJ. Bacterial community adaptation to chlorinated pollutant challenge: implications for ready biodegradation testing. [Doctoral Dissertation]. Cardiff University; 2010. Available from: http://orca.cf.ac.uk/54121/

Cardiff University

22. Caporilli, Simona. Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay.

Degree: PhD, 2010, Cardiff University

URL: http://orca.cf.ac.uk/54174/

► Vertebrate heart development involves a precise sequence of morphogenetic events from which a complex structure is formed from a linear heart tube. To study the… (more)

▼ Vertebrate heart development involves a precise sequence of morphogenetic events from which a complex structure is formed from a linear heart tube. To study the heart development in mammals is difficult because most alterations of heart structure are lethal. Therefore we use alternative model, Xenopus laevis embryos. The aim of this project is try to establish a new experimental model to help understanding the mechanism that regulates cardiac cell diversification and heart morphogenesis. In order to achieve these goals we use two assays. The cardiogenesis assay involves the use of animal cap explants excised from the animal pole of blastula embryos. It has been previously established that it is possible to induce differentiation of cardiac tissue in the same explants via the injection of GATA-4 mRNA. Here it is shown that GATA-4 reliably induces the expression of ventricular and proepicardial markers, providing an assay to study the mechanisms of cardiac cell fate diversification. However, despite these, cardiomyocytes generated in animal pole explants they do not undergo significant morphogenesis and physiological maturation. In order to study these later aspects of heart development we required a different assay in which was possible to generate a structure similar to the heart. Using GATA-4 injected AC explants transplanted into host embryos we obtained secondary beating hearts in which regionally restricted cardiac gene expression was observed in addition to growth and a limited degree of morphogenesis. We demonstrated that the host plays an essential role as it provides a wide range of permissive regions which allow the development of the SH. Moreover, we also showed that the competence to generate a secondary heart is lost in reaggregates transplanted at stage 28. The host cells however do not contribute to the SH indicating that the role of the host is providing signals which allow the development of the SH. In the future we aim to investigate the signalling pathways which mediate the host-SH interaction and the mechanism by which they allow the development of the secondary structure.

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Caporilli, S. (2010). Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/54174/

Chicago Manual of Style (16^th Edition):

Caporilli, Simona. “Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay.” 2010. Doctoral Dissertation, Cardiff University. Accessed February 27, 2021. http://orca.cf.ac.uk/54174/.

MLA Handbook (7^th Edition):

Caporilli, Simona. “Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay.” 2010. Web. 27 Feb 2021.

Vancouver:

Caporilli S. Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay. [Internet] [Doctoral dissertation]. Cardiff University; 2010. [cited 2021 Feb 27]. Available from: http://orca.cf.ac.uk/54174/.

Council of Science Editors:

Caporilli S. Investigating the mechanisms of cardiac patterning and morphogenesis using a heart formation assay. [Doctoral Dissertation]. Cardiff University; 2010. Available from: http://orca.cf.ac.uk/54174/

University of Glasgow

23. Fields, Laura Ashley. Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy.

Degree: PhD, 2013, University of Glasgow

URL: http://theses.gla.ac.uk/4755/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.586843

► Cardiac hypertrophy often develops to compensate for hemodynamic overload and therefore, in its early stages, hypertrophy is considered to be an adaptive response. Nonetheless, prolonged… (more)

▼ Cardiac hypertrophy often develops to compensate for hemodynamic overload and therefore, in its early stages, hypertrophy is considered to be an adaptive response. Nonetheless, prolonged exposure to a hypertrophic stimulus is associated with heart failure. In the heart, the compartmentalisation of the cAMP/ PKA signalling pathway plays a critical role to achieve the specificity of response and maintains regular cardiac function. Alterations in this signalling pathway have been linked to the pathophysiology of cardiac hypertrophy. Phosphodiesterases (PDEs) provide the only means of hydrolysing cAMP and therefore are essential components in the spatial and temporal control of the cAMP response. By restricting the diffusion of cAMP, PDEs prevent unspecific activation of PKA and phosphorylation of downstream targets. PDEs are therefore able to regulate the kinetics of cAMP signalling dynamics. In this study, an in vitro model of chronic catecholamine-induced cardiac hypertrophy of adult rat ventricular myocytes (ARVM) was utilised. This model allowed the investigation of the function of PDEs in regulating compartmentalised cAMP signals in cardiac hypertrophy. Using FRET-based cAMP sensor Epac1_camps fused to the unique dimerisation/docking domain sequences that anchors PKA‐RI and PKA‐RII subunits to AKAPs, this study demonstrated that, similar to neonatal rat ventricular myocytes (NRVM), adult myocytes also display restricted cAMP diffusion. These cAMP microdomains are regulated by different families of PDEs. In particular, PDE2, PDE3 and PDE4 appear to control the pool of cAMP generated in the PKA-RI compartment, whereas only PDE2 and PDE4 were found to modulate cAMP in the PKA-RII compartment in ARVM. In the in vitro cardiac hypertrophy model, a reduction in cAMP generation was detected upon β-adrenergic stimulation and altered PDE activity was visualised using FRET-based imaging. This investigation showed that PDE2 activity is significantly increased in the PKA-RII compartment of hypertrophic cardiac myocytes, while an overall reduction in PDE3 activity was detected. Immunofluorescence experiments revealed altered PDE4 localisation in hypertrophic myocytes. Advances in cyclic nucleotide signalling research, in particular of the activity and regulation of PDEs, have shown that an interaction between the cAMP and cGMP signalling pathways exists. Integration between these two pathways is mediated by the modulation of cAMP‐degrading PDEs by cGMP. Allosteric binding of cGMP to the GAF domains of PDE2 enhances its activity, whereas cGMP reduces the activity of PDE3 by acting as a competitive inhibitor. PDE2 and PDE3 therefore may act as a connection between these two signalling cascades and it is possible to predict the existence of distinct signalling units in vivo in which cGMP, by acting on PDE2 or PDE3, can selectively modulate cAMP levels. Intracellular cGMP generated by stimulation of the particulate GC (pGC) by atrial natriuretic peptide (ANP) or stimulation of the soluble GC (sGC) by the NO donor SNAP is…

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Fields, L. A. (2013). Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/4755/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.586843

Chicago Manual of Style (16^th Edition):

Fields, Laura Ashley. “Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy.” 2013. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/4755/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.586843.

MLA Handbook (7^th Edition):

Fields, Laura Ashley. “Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy.” 2013. Web. 27 Feb 2021.

Vancouver:

Fields LA. Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy. [Internet] [Doctoral dissertation]. University of Glasgow; 2013. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/4755/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.586843.

Council of Science Editors:

Fields LA. Local cAMP signalling and phosphodiesterase activity in an in vitro model of cardiac hypertrophy. [Doctoral Dissertation]. University of Glasgow; 2013. Available from: http://theses.gla.ac.uk/4755/ ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.586843

University of Glasgow

24. Malik, Natasha. Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia.

Degree: PhD, 2019, University of Glasgow

URL: http://theses.gla.ac.uk/74330/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797189

► Mechanistic target of rapamycin (mTOR) functions within a complex signalling cascade, through its activity in two unique complexes mTORC1 and mTORC2, to promote a multitude… (more)

▼ Mechanistic target of rapamycin (mTOR) functions within a complex signalling cascade, through its activity in two unique complexes mTORC1 and mTORC2, to promote a multitude of different cellular functions including autophagy, protein synthesis and survival. The exact role of these complexes during leukaemia initiation/maintenance remains to be elucidated. Here, using transgenic knockout (KO) mouse models, we determine the individual roles of mTORC1 (targeting Raptor) and mTORC2 (targeting Rictor) in normal haemopoiesis and in CLL initiation/maintenance. Our results demonstrate that mice carrying a targeted KO of Raptor at the haemopoietic stem cell (HSC) stage (Vav-Raptor KO) do not survive post birth. This is due to anaemia resulting from a significant decrease in Ter119+ population, a significant decrease in Klf1 and Klf2 gene expression, and a significant increase in the megakaryocyte-erythroid progenitor (MEP) population, suggesting a block at the MEP stage in Vav-Raptor KO foetal liver (FL). While mTORC1 plays a fundamental role in RBC development, we show that mTORC2 plays a potential role in RBC regulation, as Rictor-deficient HSPCs exhibit an increase in RBC colony formation ex vivo. Conditional KO (cKO) of Raptor (Mx1-Raptor cKO) in adult mice results in splenomegaly accompanied by increased spleen organ cellularity. Furthermore, there is a significant decrease in B cell lineage commitment, with a block in B cell development at the Lin-Sca-1+CD117+ (LSK) stage in the BM. mTORC2, on the other hand regulates late B cell maintenance as indicated by a significant decrease in transitional B cells (T1/T2), marginal zone progenitor (MZP), and follicular 1 (fol1) cells in Vav-Rictor KO mice compared to controls. To address the role of mTORC1 and mTORC2 in CLL initiation/maintenance in vitro, BM-derived haemopoietic progenitor cells (HPCs) isolated from control (cre-), Raptor-deficient (Mx1-Raptor cKO) or Rictor-deficient (Vav-Rictor KO) mice were retrovirally-transduced with a kinase dead PKCα (PKCαKR) construct to induce an aggressive CLL-like disease. Raptor-deficient BM progenitors exhibited reduced proliferation and failed to generate a CLL-like disease, due to a block in B cell lineage commitment in vitro. However, there was an increase in cell cycling and migration in PKCαKR CLL-like cells with Rictor-deficiency suggesting a role of mTORC2 in disease maintenance. To determine a role for mTORC1 in disease maintenance in vivo, NSG mice were transplanted with Mx1-Raptor control or Mx1-Raptor cKO PKCαKR transduced BM cells. Once disease was established in vivo, cKO was induced and disease load and progression was monitored. Our data demonstrate a decrease in disease load with Raptor cKO, together with a significant increase in survival. Additionally, host mice transplanted with CD19-Raptor KO PKCαKR cells exhibited a significant increase in survival. However, these mice eventually died of disease due to limitations of the KO model. Lastly, to test the translational capacity of mTOR inhibitors, efficiency of…

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Malik, N. (2019). Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/74330/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797189

Chicago Manual of Style (16^th Edition):

Malik, Natasha. “Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia.” 2019. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/74330/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797189.

MLA Handbook (7^th Edition):

Malik, Natasha. “Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia.” 2019. Web. 27 Feb 2021.

Vancouver:

Malik N. Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia. [Internet] [Doctoral dissertation]. University of Glasgow; 2019. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/74330/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797189.

Council of Science Editors:

Malik N. Elucidating the role of mTOR complexes (mTORC1 and mTORC2) in normal haemopoiesis and in Chronic Lymphocytic Leukaemia. [Doctoral Dissertation]. University of Glasgow; 2019. Available from: http://theses.gla.ac.uk/74330/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.797189

University of Glasgow

25. Rattigan, Kevin Michael. Leishmania mexicana induced perturbations of macrophage metabolism.

Degree: PhD, 2017, University of Glasgow

URL: http://theses.gla.ac.uk/8060/

► The interaction between the Leishmania parasite and the macrophage is a bidirectional one of which the outcome of is important for determining if disease progresses… (more)

▼ The interaction between the Leishmania parasite and the macrophage is a bidirectional one of which the outcome of is important for determining if disease progresses or regresses. The parasite is able to modulate the host cell at epigenetic, transcript and metabolic levels. In the context of the latter, immune metabolism is a rapidly growing area of research, and its importance in the context of normal immune function and pathology is increasingly being recognised. In this thesis a robust, untargeted metabolomics protocol has been developed in order to profile a classical in vitro model of immune metabolism, the inflammatory M1 macrophage. While previous studies use single or multiple M1 stimuli without dissecting their importance, a combinatorial approach is used here to dissect the contribution and interaction of two key M1 stimuli, interferon γ (IFNγ) and LPS. An obvious stimulus-specific response is obvious in our data. We next used this untargeted metabolomics protocol in parallel with RNAseq to examine the cost of hosting a parasite to the macrophages metabolic and transcriptional profile. By using a heat-killed control it was possible to differentiate between general immune responses and response specific to the live parasite. Additionally, a FACS protocol coupled to untargeted metabolomics was used in order to focus on the infected cell. Furthermore, the inclusion of the above mentioned M1 control revealed that either live or heat-killed Leishmania failed to elicit as strong a response. Finally, stable isotope labelled metabolomics was used to validate key findings. In summary, our untargeted metabolomics protocol has revealed immune- metabolic perturbations that are induced by IFNγ and LPS or their interaction. This information should be considered if targeting these pathways in a therapeutic context. Furthermore, by using an integrated metabolic- transcriptomics profiling approach, perturbations in glycerol-phospholipid metabolism, central carbon metabolism and arginine metabolism were found. Using stable isotope labelled metabolomics (U13C-Arginine) the current study has given unprecedented insight into how the parasite utilises this crucial amino acid, as well as confirm novel pathways.

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Rattigan, K. M. (2017). Leishmania mexicana induced perturbations of macrophage metabolism. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8060/

Chicago Manual of Style (16^th Edition):

Rattigan, Kevin Michael. “Leishmania mexicana induced perturbations of macrophage metabolism.” 2017. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8060/.

MLA Handbook (7^th Edition):

Rattigan, Kevin Michael. “Leishmania mexicana induced perturbations of macrophage metabolism.” 2017. Web. 27 Feb 2021.

Vancouver:

Rattigan KM. Leishmania mexicana induced perturbations of macrophage metabolism. [Internet] [Doctoral dissertation]. University of Glasgow; 2017. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8060/.

Council of Science Editors:

Rattigan KM. Leishmania mexicana induced perturbations of macrophage metabolism. [Doctoral Dissertation]. University of Glasgow; 2017. Available from: http://theses.gla.ac.uk/8060/

University of Glasgow

26. Kent, Robyn. Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei.

Degree: PhD, 2016, University of Glasgow

URL: http://theses.gla.ac.uk/8135/

► Plasmodium, the causative agent of malaria, has a complex life cycle requiring a mammalian host and a mosquito vector. Its cyclic infection of red blood… (more)

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Kent, R. (2016). Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8135/

Chicago Manual of Style (16^th Edition):

Kent, Robyn. “Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei.” 2016. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8135/.

MLA Handbook (7^th Edition):

Kent, Robyn. “Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei.” 2016. Web. 27 Feb 2021.

Vancouver:

Kent R. Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei. [Internet] [Doctoral dissertation]. University of Glasgow; 2016. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8135/.

Council of Science Editors:

Kent R. Experimentally inducible gametocytogenesis: a new tool to uncover the early stages of commitment in P. berghei. [Doctoral Dissertation]. University of Glasgow; 2016. Available from: http://theses.gla.ac.uk/8135/

University of Glasgow

27. Rani Ram, Asha. Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue.

Degree: PhD, 2017, University of Glasgow

URL: http://theses.gla.ac.uk/8163/

► Research aiming to understand pathogens in infection is shifting rapidly towards considering not only the individual pathogen but the whole microbial community. Therefore, understanding microbial… (more)

▼ Research aiming to understand pathogens in infection is shifting rapidly towards considering not only the individual pathogen but the whole microbial community. Therefore, understanding microbial communities through exploring the key questions in community ecology, such as the relationship between diversity and stability, are relevant here also. Research has made considerable progress in characterising microbial communities of different body sites but the human oropharynx microbiome is still among the less well known despite its importance in hosting various commensal bacteria and being an important entry site for pathogenic intrusion. Determining the healthy oropharynx microbiome will allow comparison to various disease scenarios and the attributes that change a community from a healthy to diseased state. This thesis represents the most comprehensive survey of looking at the longitudinal bacterial community structure in the oropharynx. Here, analysis was done on the bacterial oropharynx microbiome composition, its natural fluctuations and stability, and relating these to the changes that occur to the microbiome before, during and after an infection. This involved initial swabbing of the oropharynx of eighteen baseline-healthy, non-smoking participants weekly for a total period of 9 months and sequencing the V1-V2 region of the 16S rRNA gene using Illumina MiSeq sequencing. This would determine the community make up that is representative of a healthy state. This was then directly compared to oropharyngeal samples taken weekly from 12 smokers within the same age range for a total period of 6 months to observe the community differences between smokers and non-smokers. Looking at the healthy participants (non-smokers) alone, the key taxa recovered were Firmicutes at phylum level and Streptococcus, Prevotella and Veillonella at genus level; these were the most abundant taxa in healthy samples. There was variation in taxa within and between participants, but this variability in microbial community structure occurred more at genus and OTU level. Variability was influenced by changes in health status, although environmental factors were also likely to play a role even though they were not investigated here. Disturbances to the oropharynx microbiome were shown in participants that had cold-related symptoms (negative for viruses) and antibiotic treatment. These communities had decreased diversity (as opposed to high diversity healthy communities) and changes in abundances of certain taxa. However, participants recovered quickly from these disturbances (within one week after the disturbance) in that the microbiome returned to a state similar in community composition prior to the disturbance. This showed the oropharynx microbiome of baseline-healthy participants to be relatively resilient and stable as samples from the same participants were similar on a weekly basis. Looking at smokers, they had distinct changes in the bacterial community of the oropharynx in comparison to non-smoking healthy participants. This…

Subjects/Keywords: QR Microbiology

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APA (6^th Edition):

Rani Ram, A. (2017). Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8163/

Chicago Manual of Style (16^th Edition):

Rani Ram, Asha. “Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue.” 2017. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8163/.

MLA Handbook (7^th Edition):

Rani Ram, Asha. “Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue.” 2017. Web. 27 Feb 2021.

Vancouver:

Rani Ram A. Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue. [Internet] [Doctoral dissertation]. University of Glasgow; 2017. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8163/.

Council of Science Editors:

Rani Ram A. Invasions of the oropharynx: microbiome of healthy and infected respiratory tissue. [Doctoral Dissertation]. University of Glasgow; 2017. Available from: http://theses.gla.ac.uk/8163/

University of Glasgow

28. Zaki, Najad Zamirah. Quantitative proteomic responses of macrophages to Leishmania mexicana infection.

Degree: PhD, 2017, University of Glasgow

URL: http://theses.gla.ac.uk/8352/http://theses.gla.ac.uk/8352/2/2017ZakiPhDSuppl.xlsx

► The dynamics of protein turnover is central to the regulation of protein expression. The steady-state level of a protein is the net outcome of the… (more)

▼ The dynamics of protein turnover is central to the regulation of protein expression. The steady-state level of a protein is the net outcome of the change in its rate of synthesis and degradation. Different biological states or perturbations cause changes in the expression of specific proteins, which can be assessed by proteomic analysis to reveal links between genotype and phenotype. Unlike other conventional proteomic methods, which measure the amount of proteins in the system at a specific point in time, pulse-chase stable isotope labelling by amino acids in cell culture (pcSILAC) can reveal changes in the rates of protein synthesis and degradation over time. The causative agent of Leishmaniasis, Leishmania, has a digenetic lifestyle involving an extracellular flagellated promastigote living in the mid-gut of the sand fly vector and an aflagellated intracellular amastigote residing in the macrophage of the mammalian host. As they live in a different niche their protein expression could give insight into their adaptation and survival. The intricate interaction between the human host and the Leishmania parasite is key to pathology and may present new targets for chemotherapeutic development. Employing high-resolution mass spectrometry coupled with pulse-chase SILAC technique, we delved into the investigation of proteome changes in L. mexicana-infected macrophages. The first part of the thesis discusses the quantitative proteomic analysis of L. mexicana promastigote and amastigote stage. In this work, stable isotope dimethyl labelling was employed to differentially labelled promastigotes and axenic amastigotes. Our results revealed transformation from promastigote to amastigote were accompanied by: i) reduced glycolytic and gluconeogenesis pathway, ii) increased fatty acid oxidation, iii) increased mitochondrial respiration, iv) reduced expression of proteins that may have flagellar role (e.g. flagellar connector protein, flagellum targeting protein KHARON1), v) reduced stress response proteins, vi) increased protein synthesis, and vii) increased proteolytic proteins. The findings reported here substantially advance our knowledge on the differences of protein expression in different life cycle stage of L. mexicana and could be useful in finding drug targets. Another part of the thesis discusses the establishment and application of pulse-chase SILAC. In this work, a human macrophage-like cell line (THP-1) was grown in media containing L-Arg-13C6 and L-Lys-13C6 until isotope incorporation of >98% was achieved. Media was then replaced with light arginine and lysine so that light amino acids were pulsed into cells for 24 and 48 hours. In other words, protein synthesis is ‘chased’ with unlabelled amino acids. Synchronous with the switch from pulse to chase, the macrophages were infected with L. mexicana. This approach provides the ability to monitor the rates of heavy-label loss, hence determining protein degradation rates and half-lives. At 24-hour post-infection, when compared to mock-infected cells, 2016 proteins…

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Zaki, N. Z. (2017). Quantitative proteomic responses of macrophages to Leishmania mexicana infection. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8352/http://theses.gla.ac.uk/8352/2/2017ZakiPhDSuppl.xlsx

Chicago Manual of Style (16^th Edition):

Zaki, Najad Zamirah. “Quantitative proteomic responses of macrophages to Leishmania mexicana infection.” 2017. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8352/http://theses.gla.ac.uk/8352/2/2017ZakiPhDSuppl.xlsx.

MLA Handbook (7^th Edition):

Zaki, Najad Zamirah. “Quantitative proteomic responses of macrophages to Leishmania mexicana infection.” 2017. Web. 27 Feb 2021.

Vancouver:

Zaki NZ. Quantitative proteomic responses of macrophages to Leishmania mexicana infection. [Internet] [Doctoral dissertation]. University of Glasgow; 2017. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8352/http://theses.gla.ac.uk/8352/2/2017ZakiPhDSuppl.xlsx.

Council of Science Editors:

Zaki NZ. Quantitative proteomic responses of macrophages to Leishmania mexicana infection. [Doctoral Dissertation]. University of Glasgow; 2017. Available from: http://theses.gla.ac.uk/8352/http://theses.gla.ac.uk/8352/2/2017ZakiPhDSuppl.xlsx

University of Glasgow

29. Rhodes, Susan. Investigation of JAK2 targets in haematological malignancy.

Degree: PhD, 2017, University of Glasgow

URL: http://theses.gla.ac.uk/8387/

► Janus kinase 2 (JAK2) is a critical activator of signalling associated with many different receptors, particularly those associated with haematopoiesis and the inflammatory response. Classically… (more)

▼ Janus kinase 2 (JAK2) is a critical activator of signalling associated with many different receptors, particularly those associated with haematopoiesis and the inflammatory response. Classically JAK2 has been thought of as a cytoplasmic protein, but more recently there is evidence that JAK2 is able to enter the nucleus leading to alteration of epigenetic modifiers and enhancement of JAK2 transcriptional targets. This role in haematopoiesis means that alteration of JAK2 signalling, such as in malignant haematopoiesis, can be a critical factor in the development and maintenance of disease. The myeloproliferative neoplasms (MPN) are a group of conditions characterised by over-production of myeloid cells as a result of acquired mutations in haematopoietic stem cells. Two well-known MPNs are chronic myeloid leukaemia (CML), driven by the novel oncoprotein BCR-ABL, and polycythaemia vera (PV), driven by the JAK2 V617F activating mutation. JAK2 is critical for normal haematopoiesis through its role in initiating signalling following activation of a receptor by its ligand. In this study we looked several aspects of JAK2 activity, including its effect on gene expression, its activity within the nucleus, and the effect of overactivity on aspects of inflammation. Here we show that gene expression in both CML and PV patient samples is deregulated compared to normal controls with both previously confirmed alterations such as BCL2 and MCL1 in CML and STAT1 and MPL in PV, and novel alterations such as Rex1 and SUMO2 in CML and EGR1 in PV. These alterations at the level of mRNA transcription are validated by significant alterations in cell cycle and apoptosis in cell lines following treatment with JAK2 inhibitors. As part of the investigation of the activity of JAK2 in the nucleus we hypothesised that JAK2 may interact directly with PML nuclear bodies, a subnuclear structure with numerous regulatory roles in apoptosis, cell cycle, DNA repair and response to infection. Using immunofluorescence based techniques in cell lines and patient samples we showed that JAK2 does interact directly with PML nuclear bodies. This interaction was affected by JAK2 inhibitors in cell lines and increased in PV patient monocytes compared to normal controls. Treatment of cell lines with the JAK2 inhibitor ruxolitinib and arsenic trioxide, which degrades PML, led to an increase in apoptosis compared to either compound alone, suggesting a meaningful functional interaction in both normal and malignant haematopoiesis. The role of the JAK2 V617F in cellular function has been extensively investigated particularly in neutrophils and platelets. However the effect of the JAK2 V617F mutation on monocytes and monocyte derived macrophages has not previously been investigated. Here we show that patients with PV have an alteration in monocyte subsets with an increase in the inflammatory intermediate monocytes at the expense of classical monocytes. We also showed that macrophages derived from peripheral blood monocytes obtained from patients with JAK2 V617F…

Subjects/Keywords: QR Microbiology

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

APA (6^th Edition):

Rhodes, S. (2017). Investigation of JAK2 targets in haematological malignancy. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8387/

Chicago Manual of Style (16^th Edition):

Rhodes, Susan. “Investigation of JAK2 targets in haematological malignancy.” 2017. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8387/.

MLA Handbook (7^th Edition):

Rhodes, Susan. “Investigation of JAK2 targets in haematological malignancy.” 2017. Web. 27 Feb 2021.

Vancouver:

Rhodes S. Investigation of JAK2 targets in haematological malignancy. [Internet] [Doctoral dissertation]. University of Glasgow; 2017. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8387/.

Council of Science Editors:

Rhodes S. Investigation of JAK2 targets in haematological malignancy. [Doctoral Dissertation]. University of Glasgow; 2017. Available from: http://theses.gla.ac.uk/8387/

University of Glasgow

30. Gloaguen, Yoann. Supporting analysis, visualisation and biological interpretation of metabolomics datasets.

Degree: PhD, 2017, University of Glasgow

URL: http://theses.gla.ac.uk/8433/

► Over the past decades, the emerging omics technologies have enabled scientists to take a step further in the investigation of biological systems. From food safety… (more)

▼ Over the past decades, the emerging omics technologies have enabled scientists to take a step further in the investigation of biological systems. From food safety to stratified medicine, omics technologies are now an essential and powerful means to study biological processes. Omics technologies are however at different stages of maturity, and the most recent field of the omics family, metabolomics, is still in its infancy. Metabolomics attempts to catalogue, characterise and quantify all small molecules constitutive of a biological system. Liquid Chromatography - Mass Spectrometry (LCMS) is now the most commonly used technique to generate metabolomics data. The method allows the detection of hundreds of metabolites from a single sample and can provide a rapid assignment of formulae to detected masses using high accuracy mass spectrometers. While analytical methods are well developed, support for linking metabolites to detected features and interpreting the results of a data analysis in a biological context is still poorly developed. Significant challenges also arise from the additional steps required to export the data to third party environments to create a biological context. The study of integrated omics datasets as a single system has also shown to provide greater inferences than the study of each omics separately. Methods to integrate the different omics layers of biological systems are, however, at an early stage of development and no standard approach currently exists to provide a holistic view of organisms systems organisation. The objective of this thesis is to formalise, standardise and unify the data analysis of the metabolomics field, by providing to biologists the tools to support them from planning to analysis to biological impact reporting. The work presented here focuses particularly on untargeted LC-MS metabolomics approaches and attempts to assist non-expert users in performing their own analysis of metabolomics datasets. The project also aims to enable systematic biological interpretation of metabolomics datasets. The first part of the thesis focuses on creating the foundation of a unified environment for LC-MS metabolomics data analysis. Subsequently, the created environment will be expanded to integrate and support the latest technological advances in the field and provide better support for both designing studies and interpreting analysis results in a biological context. Finally, the last part of this thesis concentrates on integrating metabolomics data with other omics datasets in an attempt to provide a holistic view of a biological system.

Subjects/Keywords: QR Microbiology

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Gloaguen, Y. (2017). Supporting analysis, visualisation and biological interpretation of metabolomics datasets. (Doctoral Dissertation). University of Glasgow. Retrieved from http://theses.gla.ac.uk/8433/

Chicago Manual of Style (16^th Edition):

Gloaguen, Yoann. “Supporting analysis, visualisation and biological interpretation of metabolomics datasets.” 2017. Doctoral Dissertation, University of Glasgow. Accessed February 27, 2021. http://theses.gla.ac.uk/8433/.

MLA Handbook (7^th Edition):

Gloaguen, Yoann. “Supporting analysis, visualisation and biological interpretation of metabolomics datasets.” 2017. Web. 27 Feb 2021.

Vancouver:

Gloaguen Y. Supporting analysis, visualisation and biological interpretation of metabolomics datasets. [Internet] [Doctoral dissertation]. University of Glasgow; 2017. [cited 2021 Feb 27]. Available from: http://theses.gla.ac.uk/8433/.

Council of Science Editors:

Gloaguen Y. Supporting analysis, visualisation and biological interpretation of metabolomics datasets. [Doctoral Dissertation]. University of Glasgow; 2017. Available from: http://theses.gla.ac.uk/8433/

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Open Access Theses and Dissertations