Tesis: "Biological Sciences"

1

Wei, Fang. "The Explanatory Autonomy of the Biological Sciences". Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/16855.

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This thesis aims to argue for the explanatory autonomy of the biological sciences. According to many philosophers and scientists, the biological sciences do not have their own explanatory autonomy because they either can be reduced to other “hard” sciences such as physics and chemistry, or cannot really explain phenomena since they do not have laws of nature. To maintain the explanatory autonomy of the biological sciences, I first argue against one influential form of reductionism, i.e., explanatory reductionism, by showing that explanation in the biological sciences can be achieved without reduction. Then, I demonstrate that the biological sciences do not have laws of nature. Instead, I suggest that it is usually biological models that do the explanatory work. Given the fact that biological models usually do the explanatory work, we still need a story of how biological models can be explanatory. However, to understand how a biological model can explain phenomena in the world, we first need to understand what the model-world relationship is. To this end, a holistic view of the model-world relationship is developed by looking closely at scientific practice. Based on this, a holistic account of model explanation is proposed. The basic idea behind the holistic account of model explanation is that, for a model to be explanatory, it must answer two kinds of questions: counterfactual dependence questions (corresponding to Woodward’s what-if-things-had-been-different questions, “w-questions” for short) that concern the model itself, and hypothetical questions that concern the relationship between the model and its target system. Furthermore, I suggest that the reason a biological model can answer these two kinds of questions is due to the fact that: (a) a model is a structure, that is, a set of dependence relationships that can be employed to answer w-questions, and that (b) the holistic fit between the model and its target warrants the hypothetical inference from the model to its target and thus helps to answer the second kind of question.

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2

Burrows, Andrea C. "A social study of women in contemporary biological sciences". Diss., This resource online, 1991. http://scholar.lib.vt.edu/theses/available/etd-07282008-135540/.

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3

Edjoc, Rojiemiahd. "Movement interference effects during the tracking of biological and non biological movement". Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27840.

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Are the neural and behavioural mechanisms underlying the tracking of another human's movement different from that of tracking the movement of a non-biological system? In an experiment by Kilner, Pauligan, Blakemore, (2003) an interference effect was found during the observation and tracking of incongruent biological movements (another human performing a different action), but not so with incongruent nonbiological movements (a robot performing a different action). They defined this interference effect as the degree of change in the movement trajectory of the observer due to observed movement. Recent studies have shown that interference of this kind was subject to both biological and non biological stimuli. However, the question of whether a similar interference effect is present during the observation of movements that possess the same invariant characteristics of human movement such as minimum jerk trajectories with bell-shaped velocity profiles but are not produced by a human (Flash & Hogan, 1985) has not been previously addressed. The present experiment asked eight participants to perform vertical and horizontal movements either congruently or incongruently to novel non-biological movement stimuli sets that resemble human movement (added invariant characteristics) ranging from point light displays to 3D virtual models of humans. This was followed by an interpersonal task while tracking the movements of a human experimenter. Results demonstrated that a congruency effect was observed where incongruent human movements exhibited the most interference. In other conditions, similar congruency effects were observed where the magnitude of the interference was dependent on the biological similarity of the stimuli to actual human movement. Also a main effect of "biologicalness" (Sinusoidal vs. Sinusoidal with noise vs. Minimum Jerk), type (3d human vs. Human) and a main interaction of type and congruency (3d human vs. Human) were observed. We argue that the central nervous system is highly attuned to biological characteristics at the most deep-rooted level. It seems that biological characteristics such as movement optimality leading to the abstract representation of human movement are tightly coupled as they elicit similar interference effects as tracking movements performed by a human.

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4

Ma, Yong. "THz time domain spectroscopy and its application in biological sciences". Thesis, University of Essex, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496274.

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5

Arvestad, Lars. "Algorithms for biological sequence alignment". Doctoral thesis, KTH, Numerisk analys och datalogi, NADA, 1999. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2905.

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6

Murrel, Benjamin. "Improved models of biological sequence evolution". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71870.

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Thesis (PhD)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Computational molecular evolution is a field that attempts to characterize how genetic sequences evolve over phylogenetic trees – the branching processes that describe the patterns of genetic inheritance in living organisms. It has a long history of developing progressively more sophisticated stochastic models of evolution. Through a probabilist’s lens, this can be seen as a search for more appropriate ways to parameterize discrete state continuous time Markov chains to better encode biological reality, matching the historical processes that created empirical data sets, and creating useful tools that allow biologists to test specific hypotheses about the evolution of the organisms or the genes that interest them. This dissertation is an attempt to fill some of the gaps that persist in the literature, solving what we see as existing open problems. The overarching theme of this work is how to better model variation in the action of natural selection at multiple levels: across genes, between sites, and over time. Through four published journal articles and a fifth in preparation, we present amino acid and codon models that improve upon existing approaches, providing better descriptions of the process of natural selection and better tools to detect adaptive evolution.
AFRIKAANSE OPSOMMING: Komputasionele molekulêre evolusie is ’n navorsingsarea wat poog om die evolusie van genetiese sekwensies oor filogenetiese bome – die vertakkende prosesse wat die patrone van genetiese oorerwing in lewende organismes beskryf – te karakteriseer. Dit het ’n lang geskiedenis waartydens al hoe meer gesofistikeerde waarskynlikheidsmodelle van evolusie ontwikkel is. Deur die lens van waarskynlikheidsleer kan hierdie proses gesien word as ’n soektog na meer gepasde metodes om diskrete-toestand kontinuë-tyd Markov kettings te parametriseer ten einde biologiese realiteit beter te enkodeer – op so ’n manier dat die historiese prosesse wat tot die vorming van biologiese sekwensies gelei het nageboots word, en dat nuttige metodes geskep word wat bioloë toelaat om spesifieke hipotesisse met betrekking tot die evolusie van belanghebbende organismes of gene te toets. Hierdie proefskrif is ’n poging om sommige van die gapings wat in die literatuur bestaan in te vul en bestaande oop probleme op te los. Die oorkoepelende tema is verbeterde modellering van variasie in die werking van natuurlike seleksie op verskeie vlakke: variasie van geen tot geen, variasie tussen posisies in gene en variasie oor tyd. Deur middel van vier gepubliseerde joernaalartikels en ’n vyfde artikel in voorbereiding, bied ons aminosuur- en kodon-modelle aan wat verbeter op bestaande benaderings – hierdie modelle verskaf beter beskrywings van die proses van natuurlike seleksie sowel as beter metodes om gevalle van aanpassing in evolusie te vind.

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7

Cramer, Karla B. "Impact of constructivism via the biological sciences curriculum study (BSCS) 5E model on student science achievement and attitude". Montana State University, 2012. http://etd.lib.montana.edu/etd/2012/cramer/CramerK0812.pdf.

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The investigation involved implementing constructivist instruction via the Biological Sciences Curriculum Study 5E Instructional Model to determine its' impact on student achievement and attitude. The study included 68 seventh grade Life Science students of average to above average achievement at a community based K-12 school in Florence, Montana. Treatment was implemented during a six week biome unit in which student achievement was assessed through the Evaluation Association Measured Academic Progress and summative assessments. Student attitude was evaluated through the Test of Science Related Attitudes and learning preference surveys, pre- and post-treatment. The effectiveness of constructivism approach to instruction on achievement via the BSCS 5E Instructional Model in the science classroom was not conclusively supported by data.

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8

Au, Y. C. "Synthesising heterogeneity : trends of visuality in biological sciences, circa 1970s-2000s". Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1478180/.

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This is a case study of diagrams in a field of biological mechanism research (apoptosis), revealing that mechanism diagrams play a crucial role in the practice of developing mechanistic explanations for cell biology. This thesis supports and extends the existing literature in the following aspects: the relationship between scientific representation and practice (Daston and Galison, 2007), inter-field and inter-level integration in biological practice of mechanism research (Bechtel, 2006; Craver and Darden, 2013), and the assertive and engaging power of diagrams (Bender and Marrinan, 2010; Wood, 1992, 2010). The methodology is composed of two parts: quantitative and qualitative. The quantification draws the comprehensive patterns of diagram use via analysing the coverage of diagrams. The qualitative part analyses three layers of the diagrams: visual element, composition, and style. This part contextualises the diagrams in four senses: source of ideas, perspective, adjacent text, scope of research. The results and the interpretation of results are also composed of quantitative and qualitative parts. The quantitative part shows a noticeable prevalence of two themes of diagrams: object and mechanism. The former reflects an interest in manipulating entities. The latter reflects an interest in integration of, and interaction between, different perspectives. The relative changes in the coverage of these two themes suggest a shift in the focus of practice from manipulation of biological entities toward inter-field interaction between heterogeneous perspectives. The qualitative part contains a central argument and several interesting discoveries. The central argument is that mechanism diagrams synthesise heterogeneity and thus have the power to assert novel ideas and engage real-world practice. The heterogeneity of perspectives is embedded in the practice of developing the cell models. The term “synthesis” means that novel meanings emerge from the integration of existing perspectives. This novelty of meanings attributes to the assertive power of mechanism diagrams. The engaging power facilitates interaction amongst the component perspectives, which is an important feature of mechanism research. In sum, this argument can explain the increasing reliance upon diagrams found in the quantitative results. The other interesting qualitative discoveries include but are not limited to the following. Firstly, biological diagrams can go beyond visual resemblance to entities. Secondly, there are many creative ways of making diagrams, such as importing visual vocabulary from non-specialist areas and modular use of visual elements. These creative ways show that visual conventions in biological diagrams are not given but undergo evolution, probably responding to the growing complexity of ideas. Thirdly, the evolution of biological visualisation is not merely driven by development of technology but embodies the interaction between ideas and technological advancement. The conclusion of this study treats mechanism diagrams as both epistemological and communicative devices acting in the research dynamics. The communication is part of the processes of knowing and intervening, taking place both horizontally and longitudinally. The horizontal communication is amongst different research groups in the field. The longitudinal communication is between different stages of model developing by the same individuals. Diagrams serve in the constant defining and redefining of boundary of research arenas through bringing about new problems and activating future research.

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9

Westbrooks, Kelly Anthony. "Biological Inference using Flow Networks". Digital Archive @ GSU, 2009. http://digitalarchive.gsu.edu/cs_diss/36.

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Many bioinformatics problems are inference problems: Given partial or incomplete information about something, use that information to infer the missing or unknown data. This work addresses two inference problems in bioinformatics. The rst problem is inferring viral quasispecies sequences and their frequencies from 454 pyrosequencing reads. The second problem is inferring the structure of signal transduction networks from observations of interactions between cellular components. At first glance, these problems appear to be unrelated to each other. However, this work successfully penetrates both problems using the machinery of ow networks and transitive reduction, tools from classical computer science that prove useful in a wide array of application domains.

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10

Goldstein, Goldie L. "Smart Temporal Phase Unwrapping for Biological Objects". Diss., The University of Arizona, 2013. http://hdl.handle.net/10150/311573.

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The development of a quantitative phase microscope (QPM) has allowed the ability to acquire real-time phase movies of biological processes. The image processing of the data is critical to the system's ability to measure relative changes. The phase data must be consistent throughout a measurement and background fluctuations must be minimized. The research presented in this work discusses methods to effectively process sequences of phase data such that it can be used to quantify changes within real-time studies of living cells. This work begins by exploring two-dimensional phase unwrapping to determine the most effective ways to estimate the measured phase surface. Conventional methods of comparing unwrapping performance will be used. In addition, a novel method will be introduced that can characterize accuracy using continuity of derivatives. It will be shown that the most accurate phase estimates are made using modulation data with quality-guided phase unwrapping. After two-dimensionally unwrapping all frames of data within a measurement, there are background fluctuations due to residual surface shape as well as mean phase value fluctuations. Traditionally, manual background removal methods are implemented. Due to the large streams of data that need to be analyzed for the QPM, an automated background removal method is introduced that automatically discriminates the background from features of interest and characterizes and removes the background shape from all frames within a sequence of data. No user intervention is required and the performance rivals manual methods. The final step in processing data from a QPM is to ensure consistent phase unwrapping over an entire dataset. This is a previously undiscussed topic within the field of quantitative phase microscopy. The two-dimensional phase unwrapping methods result in reasonable phase estimates of the measured sample however there are often inconsistencies in local regions amongst sequential frames of data. This work introduces a new method, Smart Temporal unwrapping that minimizes temporal inconsistencies. The image processing methods presented in this work combine to allow phase data acquired using a QPM to quantify relative changes in biological samples. These processing steps effectively minimize errors due to system vibration, residual measurement aberration, and phase unwrapping inconsistencies.

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11

Wala, Zingfa Jantur. "Birds and people: studies based on citizen science and census data of Greater Gauteng, South Africa". Doctoral thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29541.

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Global human population growth has been predicted to grow exponentially, to a point where it exceeds the capacity of available resources to sustain it. The consequences that such exponential increase will have on the environment has also been the focus of several research. The spatial pattern of human population has reveal uneven pattern of human population with the urban areas being subject of increased influx of human population from the rural areas in search of better economic factors. The United Nations in 2007 revealed that at least half of the world’s 6.6 billion human population was living in urban areas. This number is expected to increase to over 60% of the world's population by the end of 2050. Most of this population growth is occurring in developing countries. While the health, security and town planning amongst other consequences of this global explosion in urbanization have been well-studied and documented, the impact which urbanization is having and will have on the ecosystem and on biodiversity, especially at regional and local scales has remained an a field of knowledge that has continued to evolve especially given the variable patterns and drivers of urbanization in different regions of the world as well as the different environmental factors and biodiversity in these regions. Biodiversity monitoring has been shown to be crucial to conservation goals aimed at accessing the state and condition of biodiversity. The Second South African Bird Atlas Project (SABAP2) is a citizen science atlas project which commenced in 2007. Over a decade, SABAP2 has produced a rich source of data, capturing bird distributions in South Africa. This makes SABAP2 a powerful tool for monitoring observed changes in bird communities and by extension biodiversity through time. I examined the effect that urbanization is having on the avian biodiversity in South Africa, one of the most urbanized countries in Africa. My research was focused on the 576 pentads in the four one-degree grid cells (25S 27E, 25S 28E, 26S 27E and 26E 28E) centered on the Gauteng province, referred to as Greater Gauteng region. In addition to being very urbanized, Greater Gauteng is also the most populated area in the country, and is home to 30% of the country’s 51 million people. The region is the most atlased SABAP2 region in the country, with each pentad having a minimum of 11 full-protocol SABAP2 checklists. It thus provide opportunities for the development of tools to monitor the temporal dynamics of bird communities. The first chapter is the general introduction where I did an extensive literature review of the research subject and gave an overview of the data chapters that make up the thesis. In the second chapter, I examined spatial patterns of urbanization and avian biodiversity. I assess avian species composition in the urban and rural areas of Greater Gauteng. I categorized bird data from SABAP2 for Greater Gauteng Urban and Rural subgroups. The dataset for this chapter had 700 bird species. 644 showed no range preference for either urban or rural areas. Five species showed a preference for rural areas while 51 species showed a preference for urban areas. The higher species richness recorded in urban pentads highlights the often overlooked benefits of biodiversity conservation efforts in urban areas such as green spaces and parks, gardens and water bodies. This chapter highlights the need for conservation efforts to be targeted at birds and other biodiversity in urban spaces. It is also raises the need to further promote policies aimed at having conservation efforts incorporated into town planning. In the third and fourth chapters, I used data from SABAP2 to investigate how different protected areas such as Important Bird Areas (IBAs) are to their surrounding areas by demonstrating how different the Devon Grasslands (Chapter 3) and Suikerbosrand Nature Reserve (Chapter 4) IBAs are to their immediate surrounding areas in terms of avian species richness and assemblage. Atlas data from the pentads covering these two IBAs were compared with data from the surrounding pentads. Both IBAs stand out as having more bird species than their immediate surroundings. The simple yet effective method used in this chapters can be applied in identifying potential sites for biodiversity conservation. In the fifth chapter, using a variation of the Shannon-Weiner species diversity index which is known to reach an asymptote rapidly even while species richness keeps increasing, to investigate patterns of spatial distribution of species richness and proportional diversity in Greater Gauteng. The chapter provides insights into pentads with the richest bird communities and also provides a method which can be applied to citizen science data such as SABAP2 to discover areas where particular groups of species, such as waterbirds and threatened species, are concentrated in the region. The sixth chapter examines the relationship between reporting rates of birds and human population in Greater Gauteng. With Greater Gauteng being the most populated region in South Africa, it presented an ideal situation to investigate patterns of correlation between human population and the reporting rates of bird species in the region. Based on the results obtained, the species were grouped into 18 groups categorized by the relationship pattern revealed by species reporting rates and human population. The Seventh chapter follows a similar pattern with chapter six. However, chapter seven, examines patterns between a socio-economic index, mean income per person, and the reporting rates of birds in Greater Gauteng. The eighth chapter is the conclusion. It gives a synthesis of the thesis and presents the implications for conservation of avian biodiversity in Greater Gauteng. Overall, this thesis highlights the contribution of citizen science can make to research. It also makes for a strong case showing fundamental importance of large volumes of data such as SABAP2 data, and the useful information that can be harnessed from this data. The conservation-relevant studies in the chapters of this thesis are a result of the spatial distribution patterns of the avifauna revealed by SABAP2 data from Greater Gauteng. It showed how we can detect changes in species abundance, richness and composition in a pentad or in any area, a method we can extend further to detect when bird species are starting to decline or drop out of the species list for a pentad. The results reported in this thesis provides a rich field of study for future research, especially in the field of urban ecology.

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12

Zwiessele, Max. "Bringing models to the domain : deploying Gaussian processes in the biological sciences". Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/18492/.

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Recent developments in single cell sequencing allow us to elucidate processes of individual cells in unprecedented detail. This detail provides new insights into the progress of cells during cell type differentiation. Cell type heterogeneity shows the complexity of cells working together to produce organ function on a macro level. The understanding of single cell transcriptomics promises to lead to the ultimate goal of understanding the function of individual cells and their contribution to higher level function in their environment. Characterizing the transcriptome of single cells requires us to understand and be able to model the latent processes of cell functions that explain biological variance and richness of gene expression measurements. In this thesis, we describe ways of jointly modelling biological function and unwanted technical and biological confounding variation using Gaussian process latent variable models. In addition to mathematical modelling of latent processes, we provide insights into the understanding of research code and the significance of computer science in development of techniques for single cell experiments. We will describe the process of understanding complex machine learning algorithms and translating them into usable software. We then proceed to applying these algorithms. We show how proper research software design underlying the implementation can lead to a large user base in other areas of expertise, such as single cell gene expression. To show the worth of properly designed software underlying a research project, we show other software packages built upon the software developed during this thesis and how they can be applied to single cell gene expression experiments. Understanding the underlying function of cells seems within reach through these new techniques that allow us to unravel the transcriptome of single cells. We describe probabilistic techniques of identifying the latent functions of cells, while focusing on the software and ease-of-use aspects of supplying proper research code to be applied by other researchers.

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13

Ramachandran, Gopal (Gopal Sebastian). "Modular architecture in biological networks". Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39734.

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Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2007.
Includes bibliographical references (p. 201-207).
In the past decade, biology has been revolutionized by an explosion in the availability of data. Translating this new wealth of information into meaningful biological insights and clinical breakthroughs will require a complete overhaul both in the questions being asked, and the methodologies used to answer them. One of the largest challenges in organizing and understanding the data coming from genome sequencing, microarray experiments, and other high-throughput measurements, will be the ability to find large-scale structure in biological systems. Ideally, this would lead to a simplified representation, wherein the thousands of genes in an organism can be viewed as a much smaller number of dynamic modules working in concert to accomplish cellular functions. Toward demonstrating the importance of higher-level, modular structure in biological systems, we have performed the following analyses: 1. Using computational techniques and pre-existing protein-protein interaction (PPI) data, we have developed general tools to find and validate modular structure. We have applied these approaches to the PPI networks of yeast, fly, worm, and human.
(cont.) 2. Utilizing a modular scaffold, we have generated predictions that attempt to explain existing system-wide experiments as well as predict the function of otherwise uncharacterized proteins. 3. Following the example of comparative genomics, we have aligned biological networks at the modular level to elucidate principles of how modules evolve. We show that conserved modular structure can further aid in functional annotation across the proteome. In addition to the detection and use of modular structure for computational analyses, experimental techniques must be adapted to support top-down strategies, and the targeting of entire modules with combinations of small-molecules. With this in mind, we have designed experimental strategies to find sets of small-molecules capable of perturbing fimctional modules through a variety of distinct, but related, mechanisms. As a first test, we have looked for classes of small-molecules targeting growth signaling through the phosphatidyl-inositol-3-kinase (PI3K) pathway. This provides a platform for developing new screening techniques in the setting of biology relevant to diabetes and cancer. In combination, these investigations provide an extensible computational approach to finding and utilizing modular structure in biological networks, and experimental approaches to bring them toward clinical endpoints.
by Gopal Ramachandran.
Ph.D.

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14

Holm, Tina. "Cell-penetrating peptides : Uptake, stability and biological activity". Doctoral thesis, Stockholms universitet, Institutionen för neurokemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-55664.

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Cell-penetrating peptides (CPPs) have emerged as a group of remarkable delivery vectors for various hydrophilic macromolecules, otherwise excluded from cells due to the protective plasma membrane. Unbiased conclusions regarding e.g. uptake mechanism, intracellular distribution and cargo delivery efficacy is complicated by the use of different methodological parameters by different laboratories. The first paper in this thesis introduced unifying protocols enabling comparison of results from different research groups. One of these methods, HPLC, was used in paper II to investigate CPP uptake and degradation in yeasts. Both parameters varied depending on peptide and yeast species; however pVEC emerged as a promising delivery vector in yeast since it internalized into both species tested without concomitant degradation. Protein mimicry was another investigated phenomenon and in paper III a 22-mer peptide from the p14Arf protein (Arf (1-22)) was found to be sufficient for retaining its function as a tumor suppressor. This peptide comprised a combination of apoptogenic property and CPP in one unity, thus providing opportunity to conjugate cytotoxic agents boosting the tumoricidal activity. Surprisingly, a partially inverted control peptide to Arf (1-22), called M918, was found to be an extraordinary CPP. In paper IV, it was shown to be superior to well-established CPPs in delivery of both peptide nucleic acids and proteins. Albeit the promising results these two peptides displayed, their utility in vivo, as with all peptides, is hampered by rapid degradation. With the aim of improving their stability, Arf (1-22) and M918 were synthesized with D-amino acids in the reverse order, a modification called retro-inverso (RI) isomerization. Their cell-penetrating ability was retained, but the treated cells displayed unexpected morphological alterations indicative of apoptosis. The presented results demonstrate the versatility of CPPs, functioning as vectors in both yeast and mammalian cells and as protein mimicking peptides with biological activity. Their potential as drug delivery agents is obvious; however, peptide degradation is an issue that requires further improvements before clinical success is in reach.
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 5: In press.

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15

Brooks, Daniel Stephen [Verfasser]. "The concept of levels of organization in the biological sciences / Daniel Stephen Brooks". Bielefeld : Universitätsbibliothek Bielefeld, 2016. http://d-nb.info/1082033960/34.

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16

MacNab, Wilhelmina. "A study of cognitive factors which contribute to competence in the biological sciences". Thesis, University of Glasgow, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292771.

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17

Miketova, Petra 1967. "Mass spectrometry of compounds of biological interest". Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288810.

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Mass spectrometric methods, including EI, CI, FAB and ESI LC/MS have been surveyed as tools for identification and characterization of compounds of natural origin exhibiting biological activity. Bioactive catechins isolated from green tea were analyzed by mass spectral methods: EI spectra provided both molecular weight and structural information, including epimer differentiation. FAB mass spectrometry gave both molecular weight and structural information on all compounds. ESI LC/MS provided unambiguous MW information on all compounds and some additional structural data on compounds ECG and EGCG. ESI LC/MS provided a means for separation of all compounds in a mixture and is an appropriate method for analysis of a crude extract of this plant material. Based on the result from biological testing, showing that quinic acid derivatives possess considerable anti-HIV activity, four analogs of dicaffeoylquinic acid were characterized by mass spectral methods. An attempt was made to design a mass spectral method allowing the differentiation between the analogs. FAB mass spectral analysis provided good MW information for all compounds. In addition, ions representing the elimination of water from MH+ ion of the 3,5-DCQA-OAc clearly differentiated this isomer from the 3,4-DCQA-OAc. MIKES analysis of the MH+ ions of the acetate derivative confirmed the isomer specific water loss. ESI provided unambiguous MW information on all compounds, confirming that loss of water is specific for the 3,5-DCQA-OAc. The extract of the CSF in patients with ALL was surveyed for a suitable biomarker which would indicate brain tissue damage following therapy. Phospholipid levels in CSF in three groups of patients receiving different CNS propylaxis were monitored during the course of treatment and the elevated levels were correlated to the cognitive impairment evaluation results. As a result of the CNS propylaxis, the levels of phospholipids in CSF are significantly elevated, indicating disruption of brain cell membranes. Two major classes of phospholipid were identified by FAB mass spectral analysis, PC and SM. Their elevated levels were inversely correlated with the decreased scores from cognitive testing. A close correlation was found between the PC levels and some test scores.

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18

Honti, Frantisek. "A method for the identification of biological pathways". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:e7079080-a814-431a-badd-35080f5a2825.

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Plenty of gene variants have been associated with disease, indicating widespread genetic heterogeneity, which leaves the molecular basis of complex diseases unclear. However, it is widely postulated that the products of genes whose mutations are implicated in the same disease function together in the same biological pathways and it is the disruption of these pathways that underlies the disease. Such pathways are not well defined and their identification could help elucidate disease mechanisms. To discern molecular pathways of relevance to complex disease, I have inferred functional associations between human genes from diverse data types and assessed these associations with a novel phenotype-based method. I could confirm the hypothesis that dysfunctions of genes associated with each other in terms of functional genomic and proteomic data tend to give rise to the same disease. Examining the functional association between disease-associated gene variants, I have found that genes implicated through de novo sequence variants are biased in their coding sequence length and that longer genes tend to cluster together in gene networks, leading to exaggerated p-values in functional studies. I have controlled for the confounding bias and, testing different data sources, found that an integrated phenotypic-linkage network offers superior power to detect functional associations among genes mutated in the same disease. Applying these methods to clinical phenotypes related to intellectual disability, I have observed an increased predictive potential in identifying genes associated with these phenotypes. I have also performed case–control association analyses of variants from an exome-sequencing study of Parkinson’s disease and tested the functional associations of the mutated genes. I have advanced a framework for the identification of biological pathways disrupted in complex disorders, also demonstrating the suitability of this method to functionally sub-cluster the gene variants underlying a complex disorder, with implications for the understanding of disease mechanisms.

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19

Evans, Elizabeth Balconi. "CHO-HUMAN HYBRID CELLS AS MODELS FOR HUMAN CHROMOSOME NON-DISJUNCTION". MSSTATE, 2009. http://sun.library.msstate.edu/ETD-db/theses/available/etd-03302009-124708/.

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We have used Chinese hamster ovary (CHO)-human hybrid cells containing chromosomes 16, 18, X, and 21 to test the ability of human kinetochores to successfully bind to spindle microtubules and to be distributed to the daughter cells. We have established the intrinsic rate of non-disjunction among these human chromosomes noted above and compared these rates with those in cells presented with mitotic challenges such as taxol, nocodazole, and mitosis with unreplicated genomes (MUG). Cells were grown on culture slides, fixed and processed for immunofluorescence and fluorescence in situ hybridization (FISH). Daughter pairs were identified by staining with anti-á-tubulin to identify midbodies. Human centromere DNA probes were used for FISH in order to test for the successful passage of human kinetochores to daughter cells during anaphase. Our data indicate that different human kinetochores vary in their ability to properly engage the spindle and to be successfully distributed. In addition, mitotic challenges have been shown to affect the rate of non-disjunction. The mechanism of this effect is not yet known.

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20

Peterson, Alison. "EFFECTS OF SIZE AND EXPOSURE TO PREDATION THREAT ON MATING BEHAVIOR AND PREDATION RESPONSE IN MALE WESTERN MOSQUITOFISH (GAMBUSIA AFFINIS)". MSSTATE, 2004. http://sun.library.msstate.edu/ETD-db/theses/available/etd-04022004-205940/.

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Trade offs between mating and predator avoidance advantages were studied in the western mosquitofish (Gambusia affinis: Poeciliidae). When tested with green sunfish (Lepomis cyanellus) predators, larger male G. affinis were found to have a higher number of escapes compared to smaller males. Smaller males were captured more often than larger males in groups of six and in both complex and simple habitat types. Large males, on average, were found to attempt more matings and spend a larger proportion of time near the female than smaller males. When trials with predators were compared to trials without predators, large males decreased mating attempts and time spent near the female although, small males increased time spent near females. Size of the predator did not affect these behaviors. Fry were reared under varying levels of predator exposure (visual, olfactory, both, or neither) and predation response was measured for each group at maturity. Results were not significant and were confounded by G. affinis size.

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21

Chambers, Melissa Gwen. "THE ROLE OF A NON-MICROTUBULE-BASED SPINDLE MATRIX IN EUKARYOTIC CELLULAR DIVISION". MSSTATE, 2007. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07032007-103801/.

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A non-microtubule-based spindle matrix has been observed in Drosophila melanogaster meiotic and somatic cells. This matrix comprises the proteins: Skeletor, Megator and Chromator, which localize to the nuclear periphery and chromosomes at prophase and to the microtubule spindle during mitosis and meiosis. This matrix might play a role in nuclear organization and microtubule assembly and stabilization. It is important to determine the presence or absence of this matrix in other species in order to compare form and function to that in Drosophila. These matrix proteins were studied in both normally dividing cells and cells in which division was disrupted. Our evidence suggests that a spindle matrix exists in meiocytes and embryos of the cricket, Acheta domesticus, and in a mammalian cell line established from Chinese hamster ovary cells. We report the results of our studies on the spindle matrix in invertebrate and mammalian cells and discuss implications of these findings.

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22

Johnson, Mary Kathrine. "THE METAPHASE CHECKPOINT IN CELLS UNDERGOING MITOSIS WITHOUT CHROMOSOME DUPLICATION". MSSTATE, 2007. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07062007-115810/.

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Chinese hamster ovary cells (CHO) were arrested with hydoxyurea at the beginning of DNA synthesis. Subsequent treatment with caffeine induced cells to bypass S-phase and undergo mitosis with unreplicated genomes (MUG). Treated cells built a normal spindle and distributed unattached kinetochores to daughter cells. To determine if MUG cells obey the metaphase checkpoint, we used immunoflourescence to detect and localize known metaphase checkpoint and motor proteins. In addition, the drug taxol was used to stabilize microtubules in MUG cells. The localization of CENP- E, the presence of anaphase A, taxol arrest, and taxol release acted in a similar manner as in controls. The localization of kinesin differed from the controls and that of MAD2 was inconclusive. These results imply that MUG kinetochores behave similarly to controls and probably have an operational metaphase checkpoint.

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23

Propst, Erin Althaia. "Methods of Cultivation of Hyperthermophiles that Utilize Crude Oil". MSSTATE, 2005. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07072005-222012/.

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This study demonstrated the presence of hyperthermophilic organisms in the upper Jurassic Smackover formation in Womack Hills, AL. Evidence for the presence of these organisms was shown by the cultivation of an aerobic and an anaerobic, oil-degrading hyperthermophilic culture from the cuttings of an oil well in the Jurassic Smackover at 90¢ªC. Viability of microorganisms in the formation was established through electron microscopy, by carbon dioxide production, and by protein production during incubation in medium at 90¢ªC. Not only was the presence of viable microorganisms in the reservoir established, but as a result of this study, new cultivation methods were also developed that may prove useful in future studies of these types of organisms.

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24

Lockett, Nikki Nikkia. "ANALYSIS OF REGULATORY T CELL ACTIVATION MARKERS IN FELINE IMMUNODEFICIENCY VIRUS (FIV)-INFECTED AND CONTROL PLACENTA SAMPLES FROM EARLY AND LATE TERM PREGNANCY". MSSTATE, 2009. http://sun.library.msstate.edu/ETD-db/theses/available/etd-07272009-125111/.

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Mother-to-child transmission of HIV is the leading cause of pediatric AIDS; however, mechanisms by which HIV compromises pregnancy are not understood. CD4+CD25+ T-regulatory (Treg) cells play a role in pregnancy maintenance. RNA from early and late gestation placentas and fetuses from FIV-infected and control cats were probed for expression of FIV gag and Treg markers CD25, FOXP3, and CTLA4, using real time reverse-transcriptase (RT)-PCR. High rates of vertical transmission and reproductive failure were detected in early and late pregnancy. In control animals, both FOXP3 and CTLA4 expression decreased with gestational stage, indicating a natural decline in Tregs. Expression of FOXP3 and CTLA4 was decreased at early gestation in FIV-infected queens and a trend toward decreased expression of CD25, FOXP3, and CTLA4 in placentas from FIV-infected queens producing non-viable pregnancies was observed as well. Our results suggest that FIV infection may alter placental Treg function and adversely affect pregnancy outcome.

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25

Dahal, Neeti. "OPTIMIZATION OF THE PRODUCTION OF THE LANTIBIOTICS MUTACIN 1140 IN MODIFIED M9 MEDIA". MSSTATE, 2009. http://sun.library.msstate.edu/ETD-db/theses/available/etd-10062009-145719/.

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Mutacin 1140, a class 1 bacteriocin, is produced by Streptococcus mutans and belongs to the type A lantibiotic family. Experiments were done to optimize production of mutacin 1140 in minimal media enabling a more cost efficient downstream purification method. The development of a small volume fermentation method enabled a rapid screen of several variables in a standard shaking incubator. This method provided a fast approach for determining components that promote mutacin 1140 production in minimal media broth. Lactose was determined to be the optimal carbon source for mutacin 1140 production. High concentrations of CaCl₂ (0.3% w/v) and MgSO₄ (0.77% w/v) promoted an increase in mutacin 1140 production, while ZnCl₂ and FeCl₃ appeared to impair production. Optimization of mutacin 1140 production in minimal media resulted in more than a 100-fold increase in production compared to the base medium used to begin our optimizations. The yield has been estimated by RP-HPLC to be 10 mg/L.

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26

Trueblood, Erin Donivan. "EFFORTS TOWARD UNDERSTANDING DIETARY COMPONENTS AND THE REPRODUCTIVE BEHAVIORS AND LIMITATIONS OF THE GIANT PANDA (AILUROPODA MELANOLEUCA)". MSSTATE, 2009. http://sun.library.msstate.edu/ETD-db/theses/available/etd-10212009-100838/.

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Preservation of giant pandas, Ailuropoda melanoleuca, is a worldwide concern. This study was designed to examine dietary and reproductive challenges associated with panda management. Phytoestrogens are natural plant compounds that mimic estrogen and often negatively impact mammalian reproduction. Phytoestrogens in bamboo, the pandas primary food source, is unknown. Here, estrogen radioimmuno- and receptor-binding assays revealed estrogenic activity in three species of Phyllostachys bamboo. These results present indirect evidence of phytoestrogenic mimics in bamboo, but their relevance is still unknown. Studies were also conducted to observe panda reproductive behaviors in an attempt to augment the use of an artificial vagina (AV) for semen collection. A preliminary study confirmed the panda could differentiate between estrus urine and a water control. However, when estrus urine was placed on the AV as an attractant, the subject didnt approach the AV. Further investigation of dietary challenges and reproductive alternatives are needed to substantiate these findings.

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27

Roberts, Matthew Eugene. "LONG-TERM TROPHIC SHIFTS AMONG FISHES AFTER EXTENSIVE MODIFICATION OF A SOUTHEASTERN U.S. RIVER SYSTEM". MSSTATE, 2008. http://sun.library.msstate.edu/ETD-db/theses/available/etd-10312008-135724/.

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Regulation of the Upper Tombigbee River and its incorporation into the Tennessee-Tombigbee Waterway has resulted in main-channel flows that differ from the pre-regulation condition. Flows differ in (1) magnitude: higher base flows, damped peak flows, and (2) variability: the river rises and falls faster and the number of reversals has increased. A shift in the trophic ecology of the resident fish assemblage corresponded with the altered hydrology. Assemblage-level trophic plasticity manifested through dietary shifts in species present during both time periods are coupled with changes to the taxonomic structure observed previously. Species representing the contemporary assemblage feed on fewer taxa regardless of respective trophic ecologies and include taxa that are not characteristic of diets under pre-regulation conditions. More basal resources contributing to production resulted in a greater number of trophic pathways flowing through a decreased dietary breadth. Reduced foraging efficiency is inferred for riverine specialists, possibly resulting in lower fitnesses. Tributaries are highlighted as important in maintaining biodiversity in the regulated main-channel because flows and associated trophic ecologies of resident fishes are relatively similar to those observed under pre-regulation conditions. Materials and taxa exhibit unique interactions at zones of confluence where unregulated tributaries merge with the main-channel. Quantifiable characteristics of trophic ecology and ecomorphology, along with connectance to free flowing major tributaries, emerge as potential indicators of the vulnerability of fishes to hydrologic alteration.

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28

Malachowski, Tammy L. "DEVELOPMENTAL EVOLUTION OF GENETIC REGULATION AND SIGNALING OF THE DORSOVENTRAL AXIS OF PROTOSTOMES AND DEUTEROSTOMES". MSSTATE, 2008. http://sun.library.msstate.edu/ETD-db/theses/available/etd-11042008-112347/.

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The placement of Metazoan species into correct clades has become of prime concern to the study of evolutionary development, since the most recent phylogeny of Metazoans indicates embryological divergence. Genetic regulatory networks have been extensively described for some species but not for others. This study examines possible divergence of bilaterians at the protostome-deuterostome divide by examining dorsoventral patterning genes. A specific maternally active gene, dorsal/rela, the final element in the maternal pathway, was found to be a driving force behind this divergence and was co-opted from genes already existing in the Metazoan ancestor.

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29

Kolhe, Ravindra Bharatrao. "ANGIOTENSIN II MEDIATED REGULATION OF SIGNAL TRANSDUCTION IN METABOLIC SYNDROME AND CANCER". MSSTATE, 2006. http://sun.library.msstate.edu/ETD-db/theses/available/etd-11272006-194112/.

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Patients suffering from hypertension often develop non-Insulin dependent diabetes mellitus (NIDDM), a condition caused by Insulin resistance. Though these patients have normal Insulin receptor (IR) and high levels of Insulin in blood, they fail to have IR-mediated signaling essential for glucose uptake and availability. NIDDM usually begins as insulin resistance, a condition in which Insulin Receptor (IR)-mediated signaling that leads to glucose uptake and glucose availability to cells is inhibited even in the presence of high levels of Insulin in blood. Mechanisms for the development of this Insulin resistance in patients suffering from hypertension are unclear. Angiotensin II (Ang II) hormone has been implicated in the pathogenesis of insulin resistance and inhibitors of Ang II receptor AT1 are shown to improve insulin sensitivity. Here we show that in the skeletal muscle tissue of SHR rats, Insulin Receptor (IR) beta- subunit forms a complex with the AT1 receptor and co-immunoprecipitates with IR-beta. Such strong AT1-IR association was not observed in normo-tensive rat tissue. To our knowledge this is the first report that shows AT1 can associate with IR-beta in mammalian tissue and that such association might play a role in the regulation of signaling by IR-beta. We further demonstrate that a 2-hour pre-incubation with Ang II (at concentrations 50pM to 1?ÝM) significantly inhibits 125I-insulin binding to IR in human cell line MCF-7. This effect was not seen when Ang II exposure was performed for shorter periods. The two-hour exposure to Ang II also led to the formation of a protein complex containing AT1 and IR-beta, similar to that seen in skeletal muscle tissue of SHR rats. Both AT1-IR association and differential tyrosine phosphorylation of IR-beta and associated proteins were inhibited when the cells were pre-treated with the AT1 antagonist losartan. These observations suggest that continuous presence of Ang II would result in sequestering IR in the AT1-IR complex and prevent IR from binding insulin. It also coincided with differential tyrosine-phosphorylation of IR beta-subunit and associated proteins, than that generated when IR was activated by insulin. Therefore, we infer that conformational alterations in IR caused by AT1-IR-beta association underlie the development of Ang II-induced insulin resistance. Based on these data we propose a model for AT1-mediated insulin resistance that involves receptor level interaction between the AT1 and the IR. Therefore, Insulin-independent, Ang II-induced tyrosine phosphorylation of IR prevents IR from binding Insulin and contributes to Insulin resistance. The observation that drugs that inhibit Angiotensin II converting enzyme (ACE), or activation of AT1 receptor, not only reduce hypertension, but also induce insulin sensitivity further supports the role for Ang II and AT1 in the development of NIDDM.

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30

Hellmold, Heike. "Toxicological and endocrinological aspects of cytochrome P450 in breast and lung /". Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-2787-1.

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31

Österholm, Anne-May. "Mutation profile at the HPRT locus in T-cells of non-smoking males /". Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980605oste.

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32

Lonsdale, Jemma-Anne. "Developing an estuarine planning support system : a case study for the Humber Estuary, UK". Thesis, University of Hull, 2018. http://hydra.hull.ac.uk/resources/hull:16549.

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Estuaries are often challenging to manage, as management must strike a balance between the needs of the users and the ecological and economic values within the context of multiple legislative drivers. To help facilitate integrated management, a novel Estuarine Planning Support System (EPSS) framework, using the Humber Estuary in Eastern England as a case study, has been developed. This integrated EPSS framework goes beyond previous approaches as it brings together the legislative drivers, management tools and other mechanisms for controlling plans (formal/legal management, action or work plans (e.g. shoreline management plans) and projects (a new structure or activity such as extending a port). It thereby enables managers and users to assess and address both the current environmental state, and the way in which the new project could impact an estuary in an accessible and understandable tool. This study has been primarily completed by desk based research using peer reviewed literature, technical and research reports, marine licence applications and legislation, with correspondence to several sources to determine the baseline information and existing knowledge gaps. Further to the framework, an EPSS tool was developed to provide a practical application of these requirements. The GIS-based tool ensures that the information is accessible for regulators, managers, the scientific community, developers and the public. Whilst the tool is adaptable for regions within and outside the United Kingdom (UK), the research presented in this thesis focussed on the Humber Estuary. The successful application of the tool for a complex socio-economic and environmental system such as the Humber Estuary shows that the tool can efficiently guide users through the complex administrative requirements needed to implement a management plan, and therefore support sustainable development. In addition, the tool can be used as a scoping mechanism to identify potential stressors which are to be addressed in an environmental impact assessment (EIA). The tool was validated against four case studies and was also tested by a number of stakeholders to determine the utility and accuracy of the tool. The tool was subsequently updated to reflect feedback from the stakeholders. This project should be viewed as a ‘proof of concept’ in that its primary purpose is to demonstrate the potential for developing and operationalizing an approach in the field. The method has the potential to integrate highly technical knowledge from scientists, and the views of non-scientists, to make better-informed management and planning decisions and to provide reasonable assurance to justify those decisions. The tool can be used to prevent conflicts among stakeholders and/or between uses and users and the environment, and makes it possible to integrate all the existing background data in thematic maps and identifies the human activities that use the areas, resources and services. The EPSS tool can save time and resources, aid in the decision-making process and make the decision process more transparent and consistent. It has the potential to make the governance of the marine area more logical, simple, fast and therefore more cost effective. The tool has been developed to be flexible in its approach, this means that it can be easily adapted to be used internationally and to allow for it to be adaptable to future changes. It combines the many aspects required for a holistic approach to marine management, from the inclusion of governance and stakeholder views, to the need for, and use of, monitoring information. In marine management, there will always be a need for robust and scientifically and legally defendable science to inform management. The increasingly large spatial scales that are addressed by policy makers, and the reduction in funding, means that new methods are needed to provide the evidence base which this tool helps to provide, and can be applied worldwide. The developed toolbox is an important step towards such an integrated, holistic ecosystem based approach for marine management, demonstrating that a single tool can bring together the legislative, environmental and economic considerations. The tool is a method to undertake the assessments that are currently being carried out by separate organisations, to combine in a single process that is consistent and transparent and on a quicker timescale helping to reduce costs.

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33

Ethaeb, Ali Mahdi. "Elucidation of the signalling mechanisms involved in TF-mediated apoptosis in endothelial cells". Thesis, University of Hull, 2018. http://hydra.hull.ac.uk/resources/hull:16586.

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Tissue factor (TF) is the main initiator of blood coagulation. In addition to its procoagulant property, TF has the ability to regulate various functions within cells including proliferation, angiogenesis and apoptosis. These outcomes appear to depend on the amount of TF with which the cell comes into contact with. In this study, human dermal blood endothelial cells (HDBEC) were transfected to express wild-type TF which is released following the activation of PAR2 in a normal physiological response. In addition, a model for the accumulation of TF in vascular disease and cancer was used by expressing a mutant form of TF (TFAla253-tGFP) which although expressed is not released by the cells and therefore it accumulates intracellularly. Initially, the phosphorylation of Src1 and Rac1 were monitored in order to determine any difference in phosphorylation patterns following PAR2 activation of cells. Phosphorylation of Src1, but not Rac1 was prolonged on expression of TF and was further enhanced on intracellular accumulation of TF. Therefore, the role of Src1 as a mediator of TF-induced apoptosis was examined next. Either inhibition of Src using pp60c-srcpeptide, or suppression of Src1 expression using siRNA prevented the TF-induced p38 MAPK activation and subsequent cellular apoptosis. Following confirmation of the role of Src1 in this process, an attempt was then made to delineate upstream intermediaries involved in this pathway. By using an inhibitory antibody (AIIB2), β1-integrin was shown to participate in TF-induced Src1 activation. In contrast, prevention of Src1-FAK complex formation using FAK inhibitor-14 did not interfere with the TF-mediated Src1 activation, despite a clear reduction in Src1 phosphorylation. Furthermore, TF-induced apoptosis did not appear to require Src1-FAK binding. In conclusion, this study has established further steps in the pathway by which TF can induce cellular apoptosis, and suggests a mechanism by which the increased amount of TF during inflammation can have detrimental outcome on the vascular system.

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34

Richardson, Andrew James. "Patterns of mussel bed infaunal community structure and function at local, regional and biogeographic scales". Thesis, University of Hull, 2015. http://hydra.hull.ac.uk/resources/hull:13238.

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35

Jones, Ashley. "Trace metal dynamics in mine-impacted, circum-neutral streams". Thesis, University of Hull, 2014. http://hydra.hull.ac.uk/resources/hull:11405.

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36

Lehri, Burhan. "Lactobacillus fermentum 3872 genome sequencing and analysis". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/40907/.

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In recent years, there has been a rise in antimicrobial-resistant bacteria caused by overdependence on, and misuse of, antibiotics. This has led to an increase in research for identifying alternatives to combat pathogens. One promising means of combating pathogenic bacteria, particularly for those residing in the gastrointestinal tract (GIT), is the use of probiotics. This thesis focuses on a potential probiotic strain Lactobacillus fermentum 3872, the genome sequence of which was circularised during the study, identifying genes that may contribute to probiotic activity. Several genes involved in GIT survival, such as acid symporters were discovered, along with genes that encode adhesion proteins such as those involved in mucus, fibronectin and collagen binding. The genes mentioned above may contribute to L. fermentum 3872 survivability within the GIT and have an antagonistic effect on enteric pathogens via competitive exclusion. Other interesting genes identified in L. fermentum 3872 were potentially involved in bacterial aggregation, exopolysaccharide and vitamin synthesis, along with four prophage encoding regions. Genes that encode a class III bacteriocin was also identified. An additional gene encoding a collagen binding protein (CBP) of a newly discovered plasmid pLF3872, was recognised. The chromosomal sequence also had a partial CBP encoding gene. pLF3872 has a toxin-antitoxin gene pair that ensures stable maintenance of the plasmid, along with conjugation-related genes. Functional analysis of the recombinant CBP via ELISA experiments found that the protein had the ability to bind to collagen I, a protein present on the epithelial lining of cells of the GIT. ELISA experiments also demonstrated that a common gastrointestinal pathogen, Campylobacter jejuni, can bind to collagen I in a concentration-dependent manner. In addition, mass spectrometry analysis identified that C. jejuni strains 11168H and 81-176 may utilise flagellar components (FlaA and FlaB) for adhesion. Furthermore, C. jejuni 11168H and 81-176 binding to collagen I was inhibited in the presence of either L. fermentum 3872 or CBP, thus reducing C. jejuni adherence via competitive exclusion. Using an in vitro assay, it was also demonstrated that L. fermentum 3872 cell-free supernatant could inhibit the growth of C. jejuni, due to the acidic environment brought about by L. fermentum 3872. During the completion of the genome sequence of L. fermentum 3872, comparison of various sequence assembly techniques which focused on the quality of the genome assembly was conducted. The results showed that further extension of the genome sequence during sequence assembly may lead to assembly errors when over-relying on a commonly-used sequence quality indicator, referred to as read mapping. It is suggested that care must also be taken when using long read technology to complete the genome sequence of a bacteria, as this may result in nucleotide sequence redundancies.

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37

Jaksevicius, Andrius. "Elucidation of mechanisms by which culinary herbs and spices exert their inhibitory action on the growth of CRC cells in vitro". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/41153/.

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Colorectal cancer (CRC) is one of the most commonly diagnosed types of cancer in the developed countries and the incidence is rising in the developing regions. Chronic inflammation, which is propagated by overexpression of cyclooxygenase-2 (COX-2) and its major product prostaglandin E2 (PGE2), plays a key role in the development of CRC. Culinary herbs and spices (CHS) are rich in polyphenols, have a high anti-oxidant capacity and possess anti-inflammatory activity. It has been shown that CHS inhibit the growth of CRC cells, however, their anti-carcinogenic mechanisms are mainly unknown. Hence, the aim of this study was to identify the CHS that were most potent inhibiting the growth of CRC cells, and subsequently to elucidate their anti-carcinogenic mechanisms, in particular, focusing on COX-2, the Wnt/β-catenin signalling pathway, and proteins involved in apoptosis. Another goal was to investigate whether combining the CHS would result in synergistic effects on the above. This study demonstrated that CHS extracted in water/or ethanol and their combinations inhibited CRC cell growth. This study also revealed that the most potent CHS extracted in ethanol (turmeric (TE), bay leaf (BLE) and ginger (GE)) and combinations downregulated the expression of COX-2 and suppressed COX-2 activity by reducing PGE2 release; their effect was comparable to that of the selective COX-2 inhibitor Celecoxib (50 μM). These CHS also induced apoptosis in CRC cells by targeting several key proteins: p53, caspase-3, and PAPR. However, the CHS did not have an effect on Wnt signalling pathway, which partially could be due to insufficient treatment time. In conclusion, this study demonstrated that CHS and their combinations inhibited CRC cell growth, inhibited COX-2 expression and activity, and modulated several key molecules involved in the development of CRC. Based on these findings, CHS have the potential to be utilized for CRC chemoprevention and possibly be used as a complimentary treatment. However, in vivo studies are needed to establish the true potential of these foods.

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38

Holland, Sinead. "Investigating azoreductases and NAD(P)H dependent quinone oxidoreductases in Pseudomonas aeruginosa". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/40641/.

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'Psedomonas aeruginosa' is a prevalent nosocmial pathogen predominantly associated with infections in immune compromised individuals and long term colonisation and pathogenesis in the lungs of Cystic Fibrosis patients. With multi-drug resistant strains increasingly common, the discovery of novel targets for antimicrobial chemotherapy is of utmost importance and expansion of data on 'P. aeruginosa's' complex genome could facilitate this. Azoreductases are a group of enzymes mainly noted for their reductive capacity against azo and quinone compounds. Ubiquitous amongst many classes of organism including prokaryotes and eukaryotes, the primary physiological role of azoreductases remians unclear. This study characterises azoreductase-like enzymes from 'P. aeruginosa' in terms of biochemical properties, substrate specificity and structural analysis. The effect of these enzymes on bacterial physiology in 'P. aeruginosa' is also explored in relation to antibiotic susceptibility. Three azoreductase-like genes from 'P. aeruginosa' (pa1224, pa1225 and pa4975) were overexpressed in 'E. coli' strains following molecular cloning. Recombinant proteins were biochemically characterised by means of Thin Layer Chromatography, Differential Scanning Fluorimetry and ezymatic assays. All enzymes were noted to be selective for FAD as the flavin cofactor and NADPH as the preferred reductant. All three enzymes were confirmed as NAD(P)H dependent quinone oxidoreductases (NQOs) with PA1224 also catalysing reduction of the azo substrate methyl red, albeit at a rate an order of magnitude lower than that observed for the quinone compounds. The preferred flavin cofactor for four previously characterised azoreductase and NQO enzymes (PA2280, PA2580, PA1204 and PA0949) was also explored and PA2280 and PA0949 were observed to select for FMN while PA2580 and PA1204 were selective for FAD. The crystal structure of PA2580 was solved with the nicotinamide group of NADPH bound and was noted to form a homodimer with the same short flavodoxin-like fold as previously described for other members of this enzyme family. Complemented strains of azoreductase-like gene deletion mutants of 'P. aeruginosa' PAO1 were generated via molecular cloning and used to monitor the effects of these enzymes on antibiotic susceptibility. Antimicrobial sensitivity assays were carried out and although the knockout strains displayed increased sensitivity to fluroquinolones, they did not revert to the wild type phenotype upon reinsertion of the genes of interest. This study has for the first time characterised three new NQO's from 'P. aeruginosa' PAO1 and solved the crystal structure of an azoreductase/NQO with nicotinamide bound. With these findings and a library of complemented strains generated, this original study offers a platform for the continued research into the physiological role of these enzymes.

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39

Hills, Daniel Richard. "In vitro characterisation of biological activity of novel nitric oxide donor compounds". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/40673/.

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Nitric oxide (NO), being a free radical, has a unique biological chemistry that, since its elucidation as a signaling molecule in the cardiovascular system, has been implicated in a range of diverse biological functions. Both cardiovascular disease, exacerbated by hypertension, and antibiotic-resistant bacterial infections are major yet unavoidable public health concerns. Atypical NO synthesis may be a factor these pathologies and exogenous NO may provide an alternative therapeutic strategy when endogenous NO synthesis is atypically low. Furoxans are an old, yet largely untapped resource of nitric oxide donor compounds. A panel of twelve such compounds were developed through heterocyclic synthetic chemistry and assessed for their potential biological activity. The compounds have had their NO release characterised via the Griess assay and have been investigated for both novel antibacterial and vasodilatory effects. Direct toxicity was explored using an optimised MTT assay to assess cell viability post incubation in three bacterial species: Staphylococcus epidermis, Escherichia coli, and Pseudomonas aeruginosa. The lead compound RJP06A was then exposed to bacterial biofilms, investigating its ability to prevent initial biofilm formation and promote its dispersal before determining its mechanism. Vasodilatory potential of the compounds was studied using rat thoracic aorta, pulmonary artery and renal artery. Results demonstrate that these compounds elicit a toxic effect against all three bacterial species with IC50 values ranging from 31-745 uM, which was enhanced in the presence of S-nitrosoglutathione, despite having negligible toxicity itself. Biofilm investigations of RJP06A demonstrate its ability to disperse mature single-species bacterial biofilms in a dose-dependent manner. Isometric tension data show that three quarters of the compounds produced strong, sustained relaxation of contracted aorta, and two in particular caused almost complete reversal of contraction at concentrations of 250 and 350 nM respectively. Mechanism studies suggest that the lead furoxan, RJP06A exerts its effects primarily through a cGMP-mediated NO-activated pathway, but may also have a small component whereby thiols can bypass this step and activate calcium channels directly. RJP06A has been shown to be better at inducing relaxation of resistance vessels, such as aorta, rather than pulmonary or renal artery. In both investigations, nitric oxide from RJP06A appears to be the key molecule involved in the observed effects, with scavenging evolved NO using haemoglobin attenuating its effect, and importantly the two mechanisms identified in very different models imply an evolutionarily conserved pathway of nitric oxide biology.

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40

Atkinson, Robert. "Probing cardiac metabolism in uraemic cardiomyopathy". Thesis, University of Hull, 2017. http://hydra.hull.ac.uk/resources/hull:16521.

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Cardiovascular complications are the leading cause of death in patients with chronic kidney disease (CKD). Uraemic cardiomyopathy (UCM) is characterised by structural and cellular remodelling including left ventricular hypertrophy (LVH), metabolic remodelling and mitochondrial dysfunction. Although ex vivo studies have highlighted evidence of enhanced glucose utilisation in the hypertrophied heart, cardiac glucose metabolism in uraemia has yet to be established in vivo. In addition, little is known about mitochondrial morphology or the impact of iron therapy on cardiac mitochondrial function in CKD. The aims of this study were to (I) investigate cardiac glucose metabolism in vivo using 18F-flurodeoxyglucose positron emission tomography (18F-FDG PET) during the development of UCM and (II) characterise mitochondrial morphology and the impact of iron therapy on cardiac mitochondrial function in uraemia. Experimental uraemia was induced surgically in male Sprague-Dawley rats via a subtotal nephrectomy. Dynamic PET/CT scans were acquired at 5, 9 and 13 weeks post-surgery using 18F-FDG PET. The rate and distribution of 18F-FDG uptake were determined using Patlak and polar map analysis. In a separate series of experiments the iron complex, ferumoxytol, was administered 6 weeks post-surgery and mitochondrial respiratory rates and enzyme activities determined following sacrifice 6 weeks later. Cardiac mitochondrial morphology was characterised by probing the expression of key mitochondrial fusion and fission proteins and evaluating mitochondrial size and structure in left ventricular tissue and isolated mitochondria. Renal dysfunction was prominent in uraemic animals by 12 weeks as evidenced by elevated serum creatinine, urea and the presence of anaemia. LVH was associated with moderately increased 18F-FDG uptake in the uraemic heart at 5, 9 and 13 weeks. This was paralleled at the cellular level by altered mitochondrial morphology, characterised by a more sparsely packed cristae, and increased mitochondrial state 4 respiration, indicative of reduced efficiency. However, ferumoxytol treatment did not impact on cardiac mitochondrial function at this stage of uraemia. Collectively these data suggest there is evidence of enhanced glucose utilisation in the uraemic heart in vivo and these changes are associated with altered mitochondrial structure and bioenergetics.

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41

Paudyal, Basudev. "Investigation of nanoparticles induced cell responses in the presence of innate immune factors". Thesis, Kingston University, 2018. http://eprints.kingston.ac.uk/41848/.

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Nanoparticles (NPs) are progressively being investigated for use in biomedical applications, including biological agents delivery like gene delivery, drug and protein delivery. Activation of complement pathways and interactions with immune recognition subcomponents can modulate the clearance of the NPs and subsequent inflammatory response. Such modulation could affect the intended translational applications either in the development as tissue-specific drug delivery platform or in the treatment of pulmonary diseases such as tuberculosis and lung cancer thus, poses challenges to develop them for in vivo applications. Here, we set out to study the interaction between innate immune components such as properdin, a small fragment of properdin, TSR4+5, a key lung pattern recognition molecule, surfactant protein D (SP-D), and carbon nanotubes (CNTs), and potential downstream effects on the immune response via macrophages. We report, that human properdin, an up-regulator of the complement alternative pathway and stabilizer of C3 convertase can opsonize CNTs via its thrombospondin type I repeat (TSR) 4 and 5. Uptake of properdin bound CNTs was enhanced by a macrophage cell line, THP-1, surging a robust pro-inflammatory immune response. In addition, recombinant TSR4+5 on CNTs, inhibited complement consumption, suggesting that TSR4+5, can be potentially used as a complement inhibitor in a number of pathological circumstances arising due to unintentional complement activation. Similarly, a recombinant fragment of human SP-D (rfhSP-D) bound to CNTs via its C-type lectin domain and augmented phagocytosis by THP-1 monocytic cell lines, together with an increased pro-inflammatory response. Furthermore, rfhSP-D opsozined CNTs continued to activate complement pathway via the classical pathway. Complement deposition on the rfhSP-D opsonised CNTs led to dampening of the pro-inflammatory immune response. Furthermore, like CNTs, Iron oxide nanoparticles are also recognized by complement pathway, but mainly by alternative complement pathway. Complement deposition enhanced their uptake by activated THP-1 macrophages and dampened the pro-inflammatory responses. These studies emphasise the significance of understanding the interaction between innate immune humoral factors including complement in developing nanoparticle-based drug delivery strategies.

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42

Heidari, Farshad. "In vitro modulation of host immune response by the Varicella zoster virus ORF1 gene product". Thesis, Kingston University, 2017. http://eprints.kingston.ac.uk/41971/.

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Varicella-zoster virus causes chicken pox (Varicella) primary infection, which becomes latent in the dorsal root ganglia and trigeminal ganglia, and may reactivate to cause shingles, the most serious complication of which is post-herpetic neuralgia occurring in 50% of individuals over 60 years. Severity of lesions depends on host's immune response. Like many viruses, varicella-zoster virus appears to have evolved escape mechanisms from host immune surveillance by downregulating cell surface major histocompatibility complex class 1 expression and may delay of resolution of infection. Major histocompatibility complex class 1 is processed and transported to the cell surface through the Golgi apparatus. Varicella-zoster virus genome encodes a membrane gene, open reading frame type 1, which is localised in the enoplasmic reticulum and Golgi apparatus. Given the cellular localisation of open reading frame type 1 in the Golgi apparatus, this study investigated the expression of major histocompatability complex class 1 in human immortalised keratinocytes transfected with only empty vector. As a control, the expression of major histocompatability complex class 1 human immortalised keratinocytes parental cells were also examined using current molecular biology techniques. The results of this thesis demonstrate that the expression of varicella-zoster virus-open reading frame type 1 prevents the transport of major histocompatibility complex class 1 complexes to the cell surface and causes its retention in the Golgi apparatus, which is compensated by treatment with IFN-[alpha]. Varicella-zoster virus (VZV)-open reading frame type 1 does not affect the synthesis of human leukocyte antigen class 1 heavy chains or the expression of the transporter associated with antigen processing. Additionally, we determined that varicella-zoster virus-open reading frame type 1 impedes the surface expression of human leukocyte antigen class-A and human leukocyte antigen class-B, which present viral peptides to major histocompatibility complex class I-restricted cytotoxic T lymphocytes, but not the natural killer cell inhibitory ligands human leukocyte antigen class-C and non-classical human leukocyte antigen class-E. This selective downregulation of cell surface human leukocyte antigen class 1 molecules may allow the virus to establish infection by avoiding immune clearance of virus-infected cells by both cytotoxic T lymphocytes and natural killer cells. However, it remains to be seen if open reading frame type 1 expressing cells evade cytotoxic T lymphocytes killing, through downregulation of classical major histocompatibility complex class I, and natural killer killing, through lack of downregulation of non-classical major histocompatibility complex class I. The study outcome will be a valuable attempt to elucidate factors involved in varicella-zoster virus-related lesion progression, contribute to existing knowledge, and importantly allude to further investigations on the pathogenesis of this virus on human disease. The data obtained may also offer novel means of therapeutic intervention.

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43

Robbins, Amanda. "Particle size and biotic composition on Western Cape shores, including first description of the unique fauna of pebble and cobble beaches". Master's thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33902.

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Intertidal ecology research has focused primarily on sandy (grain size < 2mm), granule (2 –< 4mm), pebble (4 –< 64mm) or cobble (64 –< 256mm) shores, and only one on the biota of boulder (256+mm) shores. This study samples intermediate shore types (1 – 256mm) within the Western Cape for the first time and compares these with published data on other Western Cape shores to determine how many distinct habitat types occur across the full spectrum of particle sizes with a focus on describing the unique fauna of pebble and cobble shores. Chapter 1 reviews the literature to date on well-studied shore types including sandy and rocky shores, and explores the limited ecological research on shore types ranging from 1 – 256mm, while both data chapters use sample data to complete the study aim. Sampled shores were surveyed using a 20 x 20cm quadrat placed at eight tidal levels along a transect from low to high shore and species collected were identified, counted and wet-weighed. Chapter 2 also used extractions from previously sampled data which included species presence, biomass and abundance per site (where available). All biomass records were converted to wet weight using published conversion factors. Chapter 2 analyzes data from 58 sites in the South-Western Cape, with data for 42 sites derived from eight previous studies, while 16 sites were sampled as part of this study. Three main groupings of sandy shores (1 – 256mm) and boulder and rocky shores (>256mm) occur. Similar to other shores within the spectrum, shores of intermediate particle grain sizes (1 – 256mm) are affected by heavy wave action, among other driving factors. Heavy wave action against intermediate grain sizes which do not have the stability of larger boulders or rocks, or the compacted nature of smaller grain sizes which can be burrowed into to protect biota, results in rough living conditions only few species can endure, as such these shores have a similar biotic composition. A polarization of species presence occurs amongst the two ends of the spectrum with mobile taxa occurring across particle grain size shores between 0.125 – 256mm, but concentrating on smaller grain sizes (256mm. Chapter 3 examines a total of 12 sites in the South-Western Cape, composed of seven pebble and five cobble shores. Of 39 taxa collected on these shores only 14 species occurred more than once and were thus considered typical of pebble and cobble shores. These were mostly air-breathing species, primarily Arthropoda and a single species of pulmonate Gastropoda. Macroalgae were notable in their absence. Unlike the burrowing species of sandy shores, or the attached species of rocky and boulder shores, pebble and cobble shore species all tended to be motile, no doubt to avoid the rolling grains. Unlike most other intertidal shores, the fauna was also concentrated towards the high shore, where food was available in the form of drift kelp, although, as some airbreathing species were found in the low shore, it is presumed some such species migrated well into the intertidal at low tide, presumably retreating back above the high-water mark at high tide.

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44

Van, Blerk Justin J. "The effect of altered rainfall seasonality on post-fire recovery of Fynbos and Renosterveld shrublands in the Cape Floristic Region". Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33950.

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Shifting climate patterns are a cause for concern for natural ecosystems globally. Of particular concern is the effect of climate change on fire-prone, Mediterranean-type shrublands globally because of the heightened sensitivity of post-fire vegetation to environmental conditions. In this thesis, I focused on investigating the relationships between rainfall seasonality patterns and post-fire vegetation processes in neighbouring Fynbos and Renosterveld shrubland communities within the mega-diverse Cape Floristic Region of South Africa. I investigated vegetation sensitivity to moisture availability at multiple levels of detail including 1) productivity and community structure, 2) growth form responses and 3) physiological performance over three years. Post-fire rainfall patterns were manipulated by artificially increasing summer rainfall and reducing winter rainfall over permanent, field sites, thus reducing annual seasonality and creating soil moisture contrasts between control and treatment plots over warm and cool seasonal periods. At all levels of investigation, postfire vegetation processes at the Fynbos site were relatively insensitive to variations in moisture availability relative to the Renosterveld site where vegetation processes and community structure were strongly affected. Nutrient limitation and lower soil tension in coarse, sandstone-derived soils of the Fynbos site could strongly limit the influence of soil moisture patterns on post-fire physiology leading to stable growth, community structure and productivity under a variety of moisture regimes. Soil moisture patterns during the first summer had significant and long-term implications for community structure and productivity patterns in the Renosterveld site, highlighting the sensitivity of vegetation patterns to early post-fire processes. Overall this study demonstrates that post-fire rainfall patterns can have strong effects on vegetation recovery processes but that structurally similar shrublands, which are specialised to differing soil types, could show marked differences in their response to climate change due to the mediation of climate responses by soils.

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45

Van, Munster Stephany. "Taxonomy and Life History of Gall Midges (Diptera, Cecidomyiidae) on Drosanthemum and Malephora (Aizoaceae) in South Africa". Master's thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33962.

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South Africa is known for its highly endemic and remarkably species-rich fauna and flora. The Greater Cape Floristic Region, consisting of the Cape Floristic Region and the Succulent Karoo Region, is home to South Africa's second most diverse plant family, the Aizoaceae. While the Aizoaceae are relatively well studied, there has been little work done on their associated insect fauna. Preliminary observations in recent years revealed a diverse community of gall midges on these plants. This study aimed to investigate the gall midges associated with two speciose genera of Aizoaceae and it is the first of its kind in South Africa. I report five new species of gall midges, three belonging to Asphondylia Loew and two to Lasioptera Meigen. These species are described from several species within the Aizoaceae genera Drosanthemum Schwantes and Malephora N.E.Br., and additional host records were recorded from Lampranthus N.E.Br., Carpobrotus N.E.br., Acrodon N.E.Br., Cephalophyllum Haw. and Jordaaniella H.E.K. Hartmann. The gall midges are described from adults, pupae and larvae and information is provided on their galls, life history and distribution. Morphological attributes of the gall midges support the description of five distinct species. Furthermore, morphological characters of the Lasioptera species described here do not fit entirely with those of the genus, suggesting that a new genus should be established for them. These results provide a mere snapshot of the gall midge diversity that is to be found on Aizoaceae in southern Africa, and much work is still to be done on the Cecidomyiidae of South Africa as a whole. Further targeted sampling may reveal greater distribution ranges and additional host plants for the five species described here, as well as many more undescribed species across the Aizoaceae.

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46

Woolley, Megan Rose. "Taxonomic and palaeobiological assessment of the South African mosasaurids". Master's thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33983.

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South African mosasaur remains consist of a frontal with articulating portions of the parietal and postorbitofrontals (SAM-PK-5265); two dentary fragments (SAM-PK-5265) assigned to ‘Tylosaurus capensis' by Broom in 1912 (SAM-PK-5265); an undescribed muzzle unit and associated isolated teeth (CGP/1/2265) from Pondoland and a more recently discovered isolated partial vertebra from St Lucia. Some research has been done on the material, but there is still uncertainty concerning their relationships and taxonomy. This research aims to provide a taxonomic assessment of all the SA mosasaurid material to better understand their phylogenetic relationships and to place them in the context of mosasaurs from other parts of Africa and globally. In addition, isotopic analyses, micro-computed tomography (micro-CT), mineralised tissue histology and scanning electron microscopy (SEM) are applied to the SA mosasaur remains to decipher various aspects of their palaeobiology. This study identifies three mosasaur taxa from SA: Mosasaurus sp., cf. M. hoffmannii., cf. Taniwhasaurus, and cf. Prognathodon. The isolated vertebra is assigned to Mosasaurus sp., cf. M. hoffmannii. The frontal and dentary fragments (SAM-PK-5265) originally described as Tylosaurus appears to be a mix of two taxa: One of the dentary fragments possesses replacement teeth with enamel ornamentation that resembles, Ta. mikasaensis, but is tentatively assigned to cf. Taniwhasaurus based on tooth recurvature. The other dentary fragment and a frontal with articulated elements are suggested to belong to the same individual as the muzzle unit for which the suggested assignment is cf. Prognathodon. Strontium analysis of tooth enamel dated the cf. Prognathodon material to the end of the Maastrichtian (87Sr/86Sr = 0.707817; age = 66.85Ma). The cf. Taniwhasaurus dentary fragment is likely Santonian-aged, as originally indicated in 1901. SEM of enamel from cf. Prognathodon reveals a complex array of prismless enamel types and pervasive aggregations of fossilised bacteria in the underlying dentine. The δ18OPO4 derived body temperature estimate (Tb) of the cf. Prognathodon (Tb = 33.21°C) compares well with previously reported Tb for mosasaurs and may indicate that the mosasaur was capable of maintaining a Tb higher than that of the surrounding seawater.

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47

Woodgate, Zoe Anne. "Determinants of predator abundance in northern KwaZulu-Natal: top-down or bottom-up?" Bachelor's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/13032.

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Includes bibliographical references.
As protected areas ultimately aim to successfully conserve natural predator populations, an understanding of the non-anthropogenic drivers of their population change is critical. Both bottom-up (e.g. food limitation, competition) and top-down (e.g. predation, interference) processes play an important role in structuring predator guilds, yet there is a poor understanding of their relative importance. Here, I investigated whether the relative abundance of mesopredators, facultative scavengers, and an apex predator were affected primarily by bottom-up processes (prey abundance) or by top-down processes (predator abundance), or a combination of the two. Central to this study was elucidating the complex relationship between mesopredators and apex predators. Caracal (Caracal caracal), blackbacked jackal (Canis mesomelas), sidestriped jackal (Canis adustus), honey badger (Mellivora capensis) and serval (Leptailurus serval) were classed together as Mesopredators. Facultative scavengers included two hyaena species (spotted Crocuta crocuta and brownhyaena Hyaena brunnea). Leopards (Panthera pardus) were included as an example of an apex predator. Data was obtained from camera-trap surveys conducted in four protected areas located in northern KwaZulu-Natal (South Africa). Results of both a nested analysis of variance and generalised linear mixed models revealed that there was no mesopredator suppression present in protected areas with complete predator guild. In addition, prey and similarly sized predator relative abundance indices (RAIs) had a significant positive effect on mesopredator, hyaena and leopard RAI. The findings suggest that bottom-up drivers are more important than top-down processes in determining the relative abundance of mammalian predators in these protected areas. My study highlights the importance of monitoring prey populations in a protected area when attempting to successfully manage mammalian predator trophic guilds.

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48

Montoya-Sanhueza, Germán Andrés. "Functional anatomy, osteogenesis and bone microstructure of the appendicular system of African mole-rats (Rodentia: Ctenohystrica: Bathyergidae)". Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/32855.

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In comparison to their ecophysiological and behavioral aspects, the skeletal system of African mole-rats (Bathyergidae) has been relatively understudied. Only a few studies have assessed their skeletal system, but these have mostly focused on their cranial and dental systems, with little attention on their postcranial skeleton. This PhD thesis provides a considerable amount of information about the functional anatomy, morphological diversity and postnatal bone morphogenesis of the appendicular system of these subterranean mammals. African mole-rats are small mammals highly adapted to the hypogeous niche that feed on underground roots and tubers. They forage, mate, breed and to some extent even disperse underground. For this, they build extensive burrow systems primarily with their chisel-like teeth, but also using their forelimbs for scratch-digging. One of the most exceptional features of bathyergids is their wide spectrum of social organization, which is unique among mammals and ranges from solitary, social and eusocial. Here, the eusocial naked mole-rat, Heterocephalus glaber, has been the most studied species. The physiology of African mole-rats is also exceptional among rodents and other mammals, showing low metabolic rates and body temperatures, as well as slow somatic growth rates. They also show enhanced fitness and prolonged longevity, features that have been associated to a life protected from both climatic extremes and predation, as well as to intergenerational transfer of information, communal care of young and shared foraging endeavors in social species. For these reasons, bathyergids represent a unique animal model to explore their skeletal adaptations to fossoriality and life underground. The aim of this research was to assess the patterns of bone growth and development to understand how adults attain their final phenotype. A comprehensive sample (N = 506) of all six bathyergid genera including seven species and comprising individuals of both sexes and of different ontogenetic stages was studied. Stylopodial (humerus and femur) and zeugopodial (ulna and tibia-fibula) bones (n = 1133) were analyzed using multiple quantitative analyses of variance (ANOVA, MANOVA), ordination (PCA, DA) and regression (RMA, OLS, equality of slopes), as well as bone labeling techniques and detailed qualitative descriptions of their midshaft bone histology. Chapter 3 shows that the specialized phenotype of the only scratch-digger bathyergid Bathyergus suillus underwent considerable morphological changes during ontogeny, e.g. juveniles showed externally more robust bones with thin cortical walls, whereas adults presented slender bones with significantly thicker cross-sections. Such changes are probably related to the increased digging demands and agonistic behaviors of the developing young. However, other aspects of their anatomy expressed perinatally, such as greater external epicondylar robustness, well-developed olecranon, teres major and deltoid processes, suggest a major role of genetic factors in their development. This chapter applied for first time the conceptualization of developmental modules to long bones, and showed that the periosteal module had higher variability and tended to grow faster than the endochondral module. Chapter 4 analyzed the morphological diversity within Bathyergidae using comparative anatomy and morpho-functional indices and showed that most species shared a highly specialized fossorial morphology and that only the naked mole-rats were morphologically divergent (having a simplified phenotype), resembling the condition of non-fossorial closest relatives of the Bathyergidae. Nevertheless, the novel inclusion of three ecomorphological categories (solitary scratch-diggers, solitary chisel-tooth diggers and social chisel-tooth diggers) in this study, showed significant differences among the groups. In general, social species appeared to have a phenotype more specialized to increase digging ability and locomotor performance, whereas solitary species showed a relatively less specialized fossorial phenotype, and a diminished locomotor ability. This may contribute to foraging strategies in social species which are known to have more complex and relatively longer burrow systems as compared to solitary species. Chapter 5 assesses the ossification patterns of the endochondral and periosteal modules, and shows that in general most bathyergids have relatively similar endochondral growth rates, irrespective of social behavior or digging strategy, although the periosteal module showed relatively higher growth rates and a higher degree of variation as compared to the endochondral module, thus appearing to be considerably less dependent on body size and genetic factors. Naked mole-rats showed the lowest growth rates among bathyergids. Considering the basal phylogenetic position of H. glaber within the family, a neotenic condition is suggested for this species, and suggests accelerated bone growth rates for the evolution of the other bathyergids. Chapter 6 provides a comprehensive description of the pattern of bone modelling in bathyergids and includes an assessment of their bone dynamics using fluorochrome labeling. All bathyergids analyzed showed increased cortical bone thickening during ontogeny, as well as low rates of endosteal bone resorption. Also, all species showed high histodiversity, limited remodeling (i.e. development of secondary osteons) and they do not ever develop Haversian bone tissues. This thesis concludes that the combination of social strategy and type of excavation had an impact on the evolution of the bathyergid appendicular system. On one hand, it was evidenced that the development of fore- and hindlimbs are not constrained by intrinsic factors (as suggested for other mammals), and that the limbs develop at similar growth rates, resulting in relatively symmetrical limb proportions. This is suggested to improve locomotion within burrows and represents an adaptation to the subterranean lifestyle, which is also observed in other fossorial mammals. This thesis further discusses how environmental factors and specific behaviors and locomotor modes, may represent strong selective pressures on limb adaptation and evolution. Similarly, a proximo-distal pattern of variation was observed, where zeugopodial elements were more variable than stylopodial elements, probably because they are in direct interaction with the substrate, so they can evolve morphological adaptations for particular habitats and locomotor behaviors. Importantly, these adaptations are most likely mediated by heterochronic modifications of their ossification modules, especially intramembranous ossification, which is known to be more responsive to environmental factors, whilst the endochondral modules would be more conservative, perhaps because a stronger genetic regulation in postnatal life. Further research on long bone modules is necessary to understand the specificity of such changes. Despite the comparatively simplified phenotype of H. glaber, they showed a larger morphospace as compared to other bathyergids, indicating a wider intraspecific variability. This agrees with previous observations suggesting skeletal plasticity for this species. It is suggested that living in large colonies results in diminished selective pressures for limb specialization but has an impact on increasing trait variability within members of the colony. This study showed that the integration of multiscale techniques and multivariate analysis of combined skeletal phenotypes (i.e. forelimb + hindlimb) offer a better understanding of adaptations to the hypogeous environment. The findings of this study also highlight the importance of considering developmental modularity of long bones for assessment of bone adaptations, particularly for understanding the differential effects of intrinsic and extrinsic factors regulating endochondral and intramembranous ossification.

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49

Mcclean, Luke Alexander. "Coevolution between brood-parasitic honeyguides and their hosts". Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/32856.

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Obligate brood parasites lay their eggs in the nests of other species, foisting the costs of parental care onto the host parents. The success of the parasite and host are then at odds, with both parties evolving defences and countermeasures in an evolutionary arms race. This reciprocal influence of acting upon both species' evolution — a process known as coevolution — has forged the natural world around us. Avian brood parasites and their hosts are now model systems for studying such coevolutionary interactions between species, providing striking examples of the adaptations that arise when the life histories of two species become entangled. In this thesis I highlight the adaptations that have arisen in response to coevolutionary selection pressures in a group of understudied avian brood parasites, the honeyguides (Indicatoridae), and their hosts. This study focuses on the greater (Indicator indicator) and lesser (I. minor) honeyguides, and their respective primary hosts, the little bee-eater (Merops pusillus) and the black-collared barbet (Lybius torquatus). The interactions between honeyguides and their cavity-nesting hosts of the Old World tropics are evolutionarily ancient, contrasting with the majority of studies of avian brood parasitism which have predominantly focused on temperate brood-parasitic species targeting open cup-nesting hosts. Therefore, honeyguides and their hosts are an ideal study system in which look for novel adaptations that have not evolved in other systems. Using field observations and experimental manipulations at each stage of the parasitic life cycle — before parasitism, during egg-laying, during incubation, and during chickrearing — I examine how honeyguides and their hosts have evolved in response to the selection pressures they exert on each other. First, in chapter two, I consider whether the nest structure of the little bee-eater – host to the greater honeyguide – can act as a defence against brood parasitism. Experimental manipulation of the size of bee-eater nest tunnels demonstrates that bee-eaters with narrower nest tunnels are less likely to be parasitized by greater honeyguides than those bee-eaters whose nests have wider nest tunnel entrances. This study provides the first experimental evidence of a host nest functioning as a frontline defence against brood parasitism. In chapter three, I take a comparative approach and use a phylogenetic framework to investigate, across multiple avian brood parasite species, the evolutionary drivers of rapid egglaying. This trait is shared by most brood-parasitic birds, but not by non-parasitic birds. I find strong evidence that the egg-laying speed of avian brood parasites is ecologically and physiologically constrained, but find no evidence that variation in the costs incurred duringparasitism events have driven variation in the rapidity of egg-laying among brood-parasitic species. In chapter four, I examine whether there are costs associated with the virulent egg puncturing behaviour of greater honeyguides, and whether honeyguides can adjust their level of virulence in accordance with these costs. I find strong support for the idea that virulence is costly to honeyguides, as bee-eater hosts are more likely to reject clutches that contained eggs punctured by honeyguides. Such punctured clutches are also more likely to be predated. Honeyguides appear to adjust how much they puncture host eggs in accordance with the severity of these costs, providing the first evidence of an avian brood parasite moderating its virulence in response to the associated costs. In chapter five, I examine egg rejection behaviour in the black-collared barbet, a common host of the lesser honeyguide. I consider whether the (smaller) size of a parasitic egg could be used as a cue for egg rejection inside the dark environment of a cavity nest. Through observations of natural parasitism events, and experimental parasitism of host nests using different sized eggs, I demonstrate that barbets are more likely to reject a clutch of eggs when they detect a small egg within the nest. This seems to be achieved through a process of true recognition, a mechanism that involves a specific innate or learnt template of what size eggs a host should reject. Barbets do not appear to rely on discordancy – comparing all eggs within their clutch in order to reject the odd one out – in order to make rejection decisions. Finally, in chapter six I explore whether honeyguides elicit additional provisioning from their foster parents by using vocal mimicry, and investigate why such extra food would be required. I demonstrate that both greater and lesser honeyguides mimic the sound of a brood of chicks of their respective hosts in order to receive higher levels of provisioning from their foster parents. I establish that greater and lesser honeyguides do this for contrasting reasons. Greater honeyguides require higher levels of provisioning to support their fast growth rate to a size much larger than their host siblings, whereas lesser honeyguides require more food in order to offset a sub-optimal diet provided to them by their foster parents.

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50

Naude, Vincent Norman. "Scale and impact of the illegal leopard skin trade for traditional use in southern Africa". Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/32936.

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While leopards (Panthera pardus) currently occupy the most extensive geographic range of all large felids, they are also suffering the highest rate of current range loss amongst large terrestrial carnivores. This is primarily because most leopards still range outside of formally protected areas where they are exposed to the full suite of anthropogenic threats affecting carnivores including habitat loss, prey depletion, conflict with humans, and commercial harvest for body parts. The extensive use of leopard derivatives among traditional healers, royalty, and culturo-religious groups poses a known but poorly understood threat to leopards. Sociopolitical sensitivities surrounding cultural identity and the illegality of much of this use have impeded an objective assessment of both the drivers and impacts of this threat. Through a multi-disciplinary approach, this thesis describes the drivers of illegal leopard skin trade among a significant portion of traditional users in South Africa, quantifies the extent of this trade across the southern African region and assesses its impact on local leopard populations. Together these findings seek to address the lack of conservation- and policy-relevant data regarding the impact and scale of the trade for traditional use in South Africa. Followers of the recently established ‘Shembe' Church, with its estimated membership of over four million in South Africa, represent the foremost culturo-religious users of illegal leopard skins in the world. Following the introduction of a faux skin alternative, I used longitudinal surveys to explore the drivers of authentic skin desirability and possession amongst faux skin recipients. While demand for authentic skins decreased, and faux alternatives were generally considered satisfactory, 27% still expressed a desire for an authentic skin, and 15% had acquired one in the three years since receiving their faux skin. Both desiring and having obtained an authentic skin were best explained by improved economic status and the perceived weakness of law enforcement. The combined demand of all Shembe followers cannot be sustained by the estimated extant leopard population of South Africa, and it is predicted that traders must be sourcing leopards from surrounding range states to meet local demands. To investigate this, I created a genetic reference database of leopards across southern Africa (1,452 individuals) and using DNA-based assignment tests, inferred the geographic origins of illegally traded skins sourced within southern Africa. Smoothed continuous assignment techniques revealed leopard source ‘hotspots' in southwestern Zimbabwe, southern Mozambique and along the eastern borders of South Africa confirming suspicions that the illegal leopard skin trade for traditional use in South Africa is transnational. A similar distribution of leopard source populations was identified from leopard parts obtained in traditional wildlife markets and a large-scale confiscation from a single trader. Together, this suggests the regional trade in leopard parts has been syndicated with predictable harvesting and trade routes into the South African consumer market. Genotyping across all trade samples (237 individuals) revealed a clear bias towards males despite reported sex-ratios being female-biased for natural free-ranging populations. To understand the ecological cost of this sex-biased exploitation of leopards, I compared the spatial, genetic, and demographic data of two South African leopard populations with markedly different histories of anthropogenic mortality. Home-range overlap, parentage assignment, and spatio-genetic autocorrelation showed that extensive historical exploitation, linked to Shembe and other traditional trade, has reduced subadult male dispersal, thereby facilitating opportunistic male natal philopatry. The resultant kinclustering in males is comparable to that of females in the well-protected reserve and has promoted localised inbreeding. Together these results demonstrate novel evidence linking significant ecological consequences to an underestimated, transnational, and syndicated illegal leopard skin trade driven by demand for traditional and religious use in South Africa. These findings are translatable to all leopard populations threatened by exploitation and emphasise the importance of long-term monitoring of leopard populations within protected areas and improving management interventions to mitigate these effects. Interventions such as anti-poaching can be focussed on the ‘hotspots' identified in this study while protected area management should prioritise the maintenance of dispersal corridors to promote in situ recovery of exploited populations. Lastly, demand reduction strategies such as the continued provisioning of suitable alternatives, together with improved education and increased enforcement, are essential to addressing the growing culturo-religious demand for leopard products contributing to the illegal harvest and trade in this iconic large predator. Success will depend on finding the balance between an improved transnational policy which effectively conserves wild leopard populations and maintaining respect for cultural practices

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