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Investigation of SH3 Domain Specificity through the Study of Cross-reactive Domains from Yeast Proteins Nbp2p and Bem1p / Investigation of SH3 Domain Specificity through the Study of Cross-reactive Domains from Yeast Proteins Nbp2p and Bem1pGorelik, Maryna 09 January 2012 (has links)
Protein interactions are often mediated through binding of protein interaction domains to short peptide motifs. However, how the specificity of interactions is regulated within domain families is not well understood. In this thesis, I investigated this issue through the study of two cross-reactive SH3 domains from the yeast adaptor proteins Nbp2p and Bem1p. Despite low sequence similarity and different cellular roles, the Nbp2p SH3 and Bem1p SH3b domains recognize targets containing the same consensus sequences, raising the question of how the specificity of these domains is controlled. The Bem1p SH3b domain is also unusual in containing a 40 amino acid long C-terminal extension required for folding and interaction with the Cdc42p GTPase, which I also investigated in this thesis.
I demonstrated that although Nbp2p SH3 and Bem1p SH3b domains recognize the same consensus sequence, each domain possesses its own unique specificity within the context of eight yeast peptides. Through structural and mutagenesis studies, I demonstrated that the Nbp2p SH3 and Bem1p SH3b domains employ different mechanism for binding, explaining how each domain can still possess its own unique specificity, while recognizing the same consensus sequence. I found that the specificity of Bem1 SH3b domain is largely regulated through inhibitory interactions, where a conserved residue in the binding interface serves to decrease binding to non-specific targets. Most significantly I observed that reducing the specificity of Bem1 SH3b domain, without reducing its binding affinity decreases its ability to function in vivo.
My structural and mutagenesis studies with the Bem1p SH3b domain also demonstrated that its C-terminal extension is involved in peptide binding surface and creates a separate surface required for interaction with Cdc42p. I also showed that the Bem1p SH3b domain is capable of simultaneously interacting with peptide targets and Cdc42p, suggesting a role for this domain in Cdc42p mediated activation.
Overall, my findings demonstrated the ability of SH3 domains to perform complex functions and bind their targets with finely tuned specificity. Most importantly, I demonstrated the significance of negative interactions for specificity determination and the importance of precise specificity for in vivo function.
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Analyses of Host Specificity, Immune Interactions and New Virulence Candidates of Pseudomonas syringaeSanina, Natali 26 February 2009 (has links)
We studied the host specificity, interactions with plant immune systems, and virulence factors of the phytopathogenic Type III secretion system-carrying bacterium Pseudomonas syringae. In studying host specificity, we ran growth and pod assays using seventeen pathovars of P. syringae on kidney bean hosts. We tracked bacterial growth numbers over six days and compared pathovar growth patterns. To study immune interactions with host plants, we performed effector-triggered immunity induction and suppression assays with individual effectors in Arabidopsis thaliana to determine whether effector evolutionary age was related to
resultant plant immune responses. No correlations were observed. To generate candidate virulence effectors, we sequenced mRNA from seven P. syringae pathovars grown in inducing media and pulled out hits to virulence-related genes.
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Molecular aspects of glutathione synthetase deficiency /Njålsson, Runa Viđarr, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.
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Coronavirus receptors and host range /Tusell, Sonia M. January 2007 (has links)
Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 198-221). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Human CDC14 phosphatases are not essential for viability : and do not regulate mitotic exit /Berdougo, Eli. January 2009 (has links)
Thesis (Ph. D.)--Cornell University, January, 2009. / Vita. Includes bibliographical references (leaves 114-122).
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A Comparison of Braden Q, Garvin and Glamorgan Risk Assessment Scales in PaediatricsAnthony, Denis, Willock, Jane, Baharestani, Mona 01 August 2010 (has links)
Aims and Objectives: To compare three risk assessment scales with respect to predictive validity Background: In paediatrics there are several competing scales and at least ten published paediatric pressure ulcer risk assessment scales have been identified. However there are few studies exploring the validity of such scales, and none identified that compares paediatric risk assessment scales. Design: Cross sectional study Methods: Three risk assessment scales, Braden Q, Garvin and Glamorgan, were compared. The total scores and sub-scores were tested to determine if children with pressure ulcers were significantly different from those with no pressure ulcer. Logistic regression was conducted to determine if the probability of developing a pressure ulcer was a better predictor of development of pressure ulcer compared with the total score of each scale. Receiver operating characteristic curves were computed and the area under the curve used to compare the performance of the risk assessment scales. Results: Data from 236 children were collected. 71 were from children in eleven hospitals who were asked to provide data on children with pressure ulcers (although seventeen did not have a pressure ulcer) of whom five were deep (grade 4). A sample of 165 were from one hospital, of which seven had a pressure ulcer, none grade four. The Glamorgan risk assessment scale had a higher predictive ability than either the Braden Q or Garvin. The mobility sub-score of each of the risk assessment scales was the most predictive in each case. Conclusions: The Glamorgan scale is the most valid of the three paediatric risk assessment scales studied in this population. Mobility alone may be as effective as employing the more complex risk assessment scale. Relevance to clinical practice: If a paediatric risk assessment scale is employed to predict risk, then unless it is valid, it may identify children who are not at risk and waste resources, or fail to identify children at risk possibly resulting in adverse health outcomes.
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Qualitative Analysis of Sequence Specific Binding of Flavones to DNA Using Restriction Endonuclease Activity AssaysDuran, Elizabeth, Ramsauer, Victoria P., Ballester, Maria, Torrenegra, Ruben D., Rodriguez, Oscar E., Winkle, Stephen A. 01 August 2013 (has links)
Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8- trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H- chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site 5′TTTAAA) but not BssHII (5′GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.
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Qualitative Analysis of Sequence Specific Binding of Flavones to DNA Using Restriction Endonuclease Activity AssaysDuran, Elizabeth, Ramsauer, Victoria P., Ballester, Maria, Torrenegra, Ruben D., Rodriguez, Oscar E., Winkle, Stephen A. 01 August 2013 (has links)
Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8- trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H- chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site 5′TTTAAA) but not BssHII (5′GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.
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A voluntary trichomonosis inter-laboratory comparison study in South AfricaZangure, Tinashe Alan January 2019 (has links)
Trichomonosis is currently the most important venereal disease of cattle in South Africa with adverse economic implications to the beef production industry due to cow abortions, infertility and culling of carrier bulls. Once diagnosed in a herd, eradication is difficult due to financial and biological implications. Bulls are asymptomatic carriers and susceptibility increases with age. In infected females, clinical signs include embryonal death, abortion, pyometra, foetal maceration and uterine discharge.
Diagnostic accuracy is one of the major clinical problems preventing easy eradication of trichomonosis from a herd and can be influenced by biological variance in the occurrence of the organism, sampling errors, sample degradation during sample transport and diagnostic laboratory inaccuracies.
This study aimed to validate the accuracy of voluntarily enrolled private (n = 8) and state-owned (n = 5) laboratories that perform trichomonosis diagnostic tests by estimating the sensitivity (Se) and specificity (Sp) per laboratory. It was hypothesized that diagnostic laboratories in South Africa play an insignificant role in the inaccuracy of the diagnosis of trichomonosis.
Laboratories performed either the culture method (n = 5), polymerase chain reaction (PCR) (n = 6) or a combination of culture and PCR (n= 2). Fresh preputial scrapings from four bulls with known negative status for trichomonosis were pooled in 200ml of phosphate buffered saline (PBS) to form the sample base for 12 subsamples of 13ml each. Duplicate subsamples were then contaminated with 2ml originating from four different laboratory cultures of Tritrichomonas foetus or 2ml of culture medium for four negative samples. Aliquots of the subsamples were transferred to an anaerobic transport medium, and the final concentration reached in these samples submitted to the laboratories, were categorised as follows: weak (<10 organisms/μl), moderate (10 – 30 organisms/μl) or strong (>30 organisms/μl). A total of 312 samples were sent by courier in two separate rounds: eight (4 duplicates) positive and four negative samples per round. Multiple logistic regression was performed on sensitivity, using sampling round, laboratory sector, diagnostic test type and sample concentration as independent variables, and removing variables in a stepwise manner based on the highest P-value.
Two public laboratories only reported on one round of sampling, and one batch of 12 samples was severely delayed in reaching another public laboratory. The sample identifications of a further two batches were not recorded by the respective private laboratories. The results from these 60 unreported samples were not included in the analysis. Laboratories that performed the PCR assay (solely, or in addition to culture) were grouped for data analysis. The overall specificity (Sp) was 100% and the sensitivity was 88.7% (95% CI 83.9% - 93.5%). Laboratories using PCR recorded higher sensitivity than those using the culture method (95.5%; 95% CI 91.0% – 99.9% and 81.3%; 95% CI 72.5% - 90.0% respectively, P < 0.01), and private laboratories recorded higher Se than public laboratories (96.4%; 95% CI 92.9% - 99.9% and 73.2%; 95% CI 61.2% - 85.2%, P < 0.01). For laboratories using PCR, weak positive samples recorded a lower sensitivity than strong positive samples (86.4%; 95% CI 70.8% - 101.9% and 100%; 95% CI 100% - 100%, respectively, P < 0.01). One public and six private laboratories obtained 100% accuracy during the two sampling rounds.
In the logistic regression model, private sector (compared to public), an increasing concentration of organisms in the sample and the second round of sampling (compared to the first round) were independent predictors of laboratory sensitivity for the detection of Tritrichomonas foetus.
It is concluded that inaccuracies in the diagnostic laboratory contributes to the deficiencies in diagnostic sensitivity for trichomonosis in South Africa, but does not influence diagnostic specificity. It is further concluded that diagnostic sensitivity was independently influenced by the sector in which the laboratory operates (private vs public) and the concentration of Tritrichomonas foetus organisms in the sample. / Dissertation (MSc)--University of Pretoria, 2019. / Production Animal Studies / MSc (Veterinary Science) / Unrestricted
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Functional Specificity of <i>Hox</i> Gene HomeoboxesZhao, Yuanxiang 11 October 2001 (has links)
No description available.
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