Dissertations / Theses: 'Mammalian models'

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Weis, Michael Christian. "Computational Models of the Mammalian Cell Cycle." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1323278159.

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2

Rabani, Michal. "Models of dynamic RNA regulation in mammalian cells." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/84894.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 135-142).
Complex molecular circuits, consisting of multiple intertwined feedback loops and non-linear interactions, are a hallmark of every living cell, and a model of a dynamic complex network. Here, I systematically study the dynamic changes in the cellular circuits that control RNA levels in mammalian cells, focusing on the model response of immune dendritic cells to pathogens, through an integration of comprehensive computational models and innovative empirical approaches. I establish a computational framework to follow the dynamics of processes for RNA birth (production, by transcription), maturation (processing), and death (degradation), and their integration in the dynamic RNA life cycle. I study the kinetics of a gene's RNA population with a model of its production and degradation, and generalize the system as an ensemble of genes. I further model genes as composite particles and study the regulation and kinetics of altering their internal structure. To allow robust statistical inference from these models, I develop innovative laboratory assays and collect extensive experimental data on the system. I directly measure RNA production rates by coupling short RNA metabolic labeling with advanced RNA quantification. I leverage recent improvements in RNA quantification by next-generation sequencing technology, to significantly increase the resolution of metabolic labeling in both time and gene-structure. Finally, I collect perturbation data, by monitoring RNA levels when specific elements of the network are disabled. In this way, I formulated several general principles of RNA regulation and its temporal evolution in mammalian cells. I find that temporal changes in production provide a dominant input in computing RNA levels by the cell over time. Yet, dynamic degradation changes contribute to shaping expression peaks, and dynamic processing changes allow a fast accumulation of mature transcripts. Static degradation and processing rates vary between genes and between individual splicing junctions, consistently with their function and expression dynamics. This study is broadly applicable to many normal as well as diseases misregulated cellular networks, and is also relevant for a more general analysis of complex systems dynamics.
by Michal Rabani.
Ph.D.

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3

Shaw, Alexander George. "Developing models of the mammalian cell S phase." Thesis, University of Manchester, 2011. https://www.research.manchester.ac.uk/portal/en/theses/developing-models-of-the-mammalian-cell-s-phase(3df7caaf-fd64-4bd2-b500-802f1a2c8ce2).html.

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The accurate replication of the mammalian genome is a complex and logistically challenging process. The entirety of the genome must undergo a single duplication with as little error as possible. This must occur in a coordinated fashion and over suitably short time scale so as to allow timely cellular division within a cell cycle that is typically around 24 hours in a human cell. A great wealth of knowledge already exists describing various aspects of the S phase, during which this replication of the genome occurs. This data has been gathered over a variety of model systems, ranging from inferences from the replicative mechanics of SV40 through to direct observations of replication in mammalian cells.In order integrate this data and determine the value of inferences from different data sources, quantitative models of the mammalian cell S phase are required. This study documents the development of several such models and the exploration of the influences that experimentally determined parameters and different mechanistic theories can have on the behaviour of a simulated S phase. Of particular exploratory interest were the modes of activating replication of replicon clusters, with the aim of simulating experimentally observed dynamics. Additionally, the study also aimed to investigate the variation of replication fork rates and the density of origins of replication, along with the relationship that occurs between the two during both replicational stress and during a normal S phase. Through an iterative series of models, relevant parameters and key theories are sequentially explored so as to better understand the S phase. Particularly influential parameters were identified and studied in detail, with experimental determination where necessary in order to more accurately inform the model system. Conclusions concerning the behaviour of the system and the potential impact of the results were drawn upon the completion of each level of modelling and experimental work.To conclude the study, a linear model simulating the genome of the MRC5 cell line was used to estimate the modes activation of DNA replication along chromosomes in order to recreate experimentally observed replication dynamics. Experimentally determined profiles of replication fork rates and the density of origin firing were also determined for the MRC5 cell line, and were used to populate the model with accurate and appropriate data. Using the model to simulate S phase through a variety of behavioural parameters, realistic S phase dynamics were found to occur through a combination of de novo activation of replicon clusters and a specific probability of neighbour activation by completed clusters. These derived mechanics, when performed on a system correctly parameterised with suitable data, can simulate experimentally observed phenomena. The development of the model highlighted the requirements of data fit for purpose, and the study also stresses the need for critical consideration of inferences made between different model systems.

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Patel, Nirmal Praful School of Medicine UNSW. "Olfactory progenitor cell transplantation into the mammalian inner ear." Awarded by:University of New South Wales. School of Medicine, 2006. http://handle.unsw.edu.au/1959.4/26180.

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A practical consideration in the development of cellular therapy technology for the inner ear is the development of an in vitro model for assessing the optimal conditions for successful application of cells. The first part of this thesis describes the adaptation of the cochleovestibular structure harvested from P1 mouse pups for analysis of factors critical for the optimal implantation of stem cells in the inner ear. Results of these studies establish that the c17.2 neural stem cell line can be introduced into the cochleovestibular structure in vitro. Using this model, c17.2 cells demonstrated survival predominantly within the vestibule and basal spiral ganglion regions. Furthermore, the addition of the ototoxin, cisplatin and the neurotrophin, Brain Derived Neurotrophic Growth Factor (BDNF) enhanced the survival and migration/dispersion of c17.2 cells within the cochleovestibular explant. The second part of this thesis examines the hypothesis that olfactory neurosphere (ONS) and progenitor cells harvested from the olfactory epithelium represent a viable source of graft material for potential therapeutic applications in the inner ear. Olfactory epithelium represents a unique source of pluripotent cells that may serve as either homografts or autografts. The feasibility of ONSs to survive and integrate into a mammalian cochlea in vivo was assessed. The ONSs were isolated as a crude fraction from the olfactory epithelium of P1 to P3 day old swiss webster mouse pups, ubiquitously expressing the Green Fluorescent Protein (GFP) marker. The ONSs were microinjected into the cochleae of adult CD1 male mice. Four weeks following their implantation, ONS cells expressing the GFP marker and stained by Nestin were identified in all areas of the cochlea and vestibule, including the spiral ganglion. Robust survival and growth of the implanted ONS and ONS derived cells in the cochlea also included the development of ???tumor-like??? clusters, a phenomenon not observed in control animals implanted with c17.2 neural stem cells. Collectively, the results of this thesis illustrate the potential of olfactory neurosphere and progenitor cells to survive in the inner ear and expose a potential harmful effect of their transplantation.

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Nel, Maria Elizabeth. "Mammalian cell cultures as models for metabolomic studies / Nel Z." Thesis, North-West University, 2012. http://hdl.handle.net/10394/8205.

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The use of cultured cells in metabolomic studies is receiving more and more attention. There are many advantages when using cultured cells in metabolomic studies, for example cultured cells can easily be manipulated for the purpose of the experiment. This creates many opportunities for metabolomics studies, for example cell cultures can offer an alternative manner of drug testing. Even though the use of cultured cells in metabolomic studies is very promising and they create many opportunities for metabolomic research, there are still challenges that create obstacles in this research. One of the challenges is that present analytical technologies do not always fully meet the requirements for metabolomics. There is, however, much effort going into optimising the methods concerning cultured cells and metabolomics, but there is a lack of attention when it comes to the sample preparation which is initiated by quenching. The aim of this study was to investigate cultured cells as models for metabolomics investigations and to standardise a proper quenching method for a metabolomics analysis of mammalian cultured cells. A quenching method adapted from the literature was evaluated for the cell line used in this study, namely HeLa. Metabolites of the central carbon metabolism were targeted, using a published list. This method was tested for its effectiveness by introducing the samples to waiting periods (0, 3, 6 and 24 hours) before extraction after immediate quenching. Results indicated that the entire metabolism under study was not effectively quenched. The optimum composition and temperature for this quenching method were also investigated by comparing three different quenching methods derived from the literature. The results were contradicting. Cell cultures were exposed to two perturbations (environmental and genetic) to investigate if these perturbations can be captured and measured by using metabolomics as an instrument. There was a significant difference between control groups and the groups exposed to the different perturbations. The results gained from this study indicate that it is definitely possible to use cultured cells in metabolomics studies.
Thesis (MSc (Biochemistry))--North-West University, Potchefstroom Campus, 2012.

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6

Hayes, Chris. "Genetic and functional analysis of mammalian limb development." Thesis, University of Oxford, 1998. http://ora.ox.ac.uk/objects/uuid:1443b218-fb63-4ced-9b15-e81947448ced.

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7

Siepel, Adam C. "Comparative mammalian genomics : models of evolution and detection of functional elements /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2005. http://uclibs.org/PID/11984.

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8

Dalle, Pezze Piero. "Dynamical models of the mammalian target of rapamycin network in ageing." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2183.

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The mammalian Target of Rapamycin (mTOR)kinase is a central regulator of cellular growth and metabolism and plays an important role in ageing and age- related diseases. The increase of invitro data collected to extend our knowledge on its regulation, and consequently improve drug intervention,has highlighted the complexity of the mTOR network. This complexity is also aggravated by the intrinsic time-dependent nature of cellular regulatory network cross-talks and feedbacks. Systems biology constitutes a powerful tool for mathematically for- malising biological networks and investigating such dynamical properties. The present work discusses the development of three dynamical models of the mTOR network. The ﬁrst aimed at the analysis of the current literature-based hypotheses of mTOR Complex2(mTORC2)regulation. For each hypothesis, the model predicted speciﬁc diﬀerential dynamics which were systematically tested by invitro experiments. Surprisingly, nocurrent hypothesis could explain the data and a new hypothesis of mTORC2 activation was proposed. The second model extended the previous one with an AMPK module. In this study AMPK was reported to be activated by insulin. Using a hypothesis ranking approach based on model goodness-of-ﬁt, AMPK activity was insilico predicted and in vitro tested to be activated by the insulin receptor substrate(IRS).Finally,the last model linked mTOR with the oxidative stress response, mitochondrial reg- ulation, DNA damage and FoxO transcription factors. This work provided the characterisation of a dynamical mechanism to explain the state transition from normal to senescent cells and their reversibility of the senescentphenotype.

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9

Roopra, Avtar. "Transcriptional control of the m4 muscarinic receptor gene : mammalian and yeast models." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313823.

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10

Zaksauskaite, Ringaile. "Analysis of chromosomal protein-linked break repair in zebrafish and mammalian models." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/20765/.

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Crosatti, Marialuisa. "Use of non-mammalian models to assess the virulence of Pseudomonas aeruginosa." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/32941.

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Pseudomonas aeruginosa (P. aeruginosa) is the archetypical opportunistic pathogen that accounts for significant numbers of cases of hospital-acquired infections. It adapts to diverse environments in part because it may “modify” its genome through horizontal gene transfer (HGT). Caenorhabditis elegans (C. elegans) and Acanthamoeba spp. (A. castellanii and A. polyphaga) can be employed as in vivo surrogates to investigate the virulence associated with P. aeruginosa clinical isolates and with the presence of genomic islands, genetic elements acquired through HGT. A PA14 based P. aeruginosa pathogenicity island (PAPI)-2 minus mutant exhibited only a minor reduction in virulence as measured by C. elegans survival using the slow-killing assay (SKA) model of virulence but significant attenuation of virulence was found as assessed by the expansion of A. castellanii but not A. polyphaga film on non-nutrient agar. A C. elegans highthroughput assay (HTA) was also established as model of infection and validated against the SKA. The HTA was employed to screen a panel of P. aeruginosa mutants created by deletion of tRNA-associated genomic islands. Few mutants (5 out of 21) showed attenuated virulence toward C. elegans in HTA many of which were confirmed to be less virulent toward the nematode using SKA. Screening of clinical isolates linked the strains isolated from blood culture of a patient with lower survival of C. elegans in HTA compared with strains isolated from sputum. Moreover, type III secretion system effector (T3SS) exoU-positive strains and strains developing pigments during growth were more virulent toward C. elegans in HTA than T3SS effector exoS-positive strains and pigment-less strains, respectively. Since pigment development was also linked to exoU and this gene has been associated with genomic islands integrated at tRNALys10, it was inferred that these genomic islands may bear functions affecting C. elegans survival possibly enhancing iron scavenging.

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12

Guilliatt, Andrea Marie. "Expression of Von Willebrand Factor in mammalian cell lines as models of Von Willebrand's Disease." Thesis, University of Sheffield, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284766.

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13

Hwang, Dick G. "Bayesian Markov chain Monte Carlo phylogenetic analysis of mammalian evolution reveals varying substitution patterns along the sequence and across lineages /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/10294.

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14

Lupi, Daniela. "The entrainment pathway of the mammalian circadian system : a study of retinally degenerative and normal rodent models." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368088.

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15

Thompson, Airlia Camille Simone. "Mediators and markers of mammalian lifespan extension| Proteomic, proliferative and hormonal adaptations in mouse models of extended lifespan." Thesis, University of California, Berkeley, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3640662.

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Aging is broadly defined as the deterioration of bodily tissues over time. Excluding death due to infectious disease or accidents, aging is what ultimately places finite limits on lifespan and healthspan, the time in which in individual remains active and in good health. Although healthspan and lifespan are intimately linked, it is the extension of human healthspan that is a major goal of gerontological research. Such an achievement would have broad social and economic benefits and importantly would mitigate the dire consequences of the predicted future rise in the prevalence of age-related diseases due to the growing proportion of the population that is of advanced age (65yr and over). A broad understanding of the physiological, metabolic, hormonal, cellular and molecular factors that contribute to aging and lifespan determination will allow for the development of strategies to extend healthspan.

The work presented herein describes the use of three unique mouse models of extended healthspan and maximum lifespan, including calorie restricted (CR), Snell Dwarf and rapamycin-treated mice, to investigate several factors linked to healthspan and lifespan determination in mammals. These factors include reduced insulin-like growth factor-1 (IGF-1) expression, reduced cell proliferation, reduced protein synthesis and enhanced proteome stability. Using these three models the following conclusions have been drawn: 1) Physiological adaptations to CR previously suggested to confer the healthspan and lifespan benefits of CR in rodents cannot account for the global cell proliferation rate-lowering effect of CR; 2) Fibroblast growth factor 21 (FGF21) is not necessary for the reduction in IGF-1 or the reduction in global cell proliferation rates in response to moderate CR in adult mice; 3) A reduction in global cell proliferation rates is not a consistent predictor of maximum lifespan extension in mice; 4) A reduction in hepatic protein replacement rates is a sensitive and early predictor of maximum lifespan extension in mice and likely reflects a more stable and functional proteome.

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Abdallah, Hussein(Hussein M. ). "The core mammalian pluripotency network in induced pluripotent stem cell (iPSC) formation : models for genetic and epigenetic reprogramming." Thesis, Massachusetts Institute of Technology, 2018. https://hdl.handle.net/1721.1/122910.

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This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2018
Cataloged from student-submitted PDF version of thesis. "February 2018."
Includes bibliographical references (pages 23-37).
In 2006, history was made in a seminal experiment that converted mouse fibroblasts to a pluripotent phenotype coined the 'induced pluripotent stem cell' (iPSC) state. Unhindered by ethical or immunogenic constraints, iPSCs potentially hold the keys to tremendous applications in therapeutic and regenerative medicine. Furthermore, on-demand iPSC generation has the capacity to revolutionize basic research in disease modeling and drug discovery. These promises notwithstanding, the economics of iPSC formation--which remains a slow, inefficient, expensive, and laborious process--still stand in the way of fully making use of this extraordinary technology. In this thesis, I present mathematical models aimed at understanding the theoretical reprogrammability of the core pluripotency gene regulatory network being awakened in iPSC reprogramming. Using these modeling insights, I discuss the merits of current reprogramming strategies, which can be viewed as open-loop perturbations in control theoretic terms. I then discuss an alternative paradigm of closed-loop reprogramming, which is theoretically shown to be far superior when it comes to the reprogrammability of the pluripotency network. Finally, I propose a reprogramming model that incorporates the eæect of DNA demethylation on the activation of the network, with attention given to the relationship between this epigenetic transformation and the cell proliferation barrier that somatic cells seemingly face on the road to pluripotency.
by Hussein Abdallah.
M. Eng.
M.Eng. Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science

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17

Klöting, Nora. "Phenotypic and genetic analysis in animal models and humans with type 1 diabetes or metabolic syndrome: unraveling complex mammalian diseases." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=974087254.

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18

Marta, Mónica Sofia Calado. "Gene regulation and immune mechanisms in multiple sclerosis experimental models /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-280-4/.

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19

Hayes, Samuel Lee. "Response of mammalian models to exposure of bacteria from the genus Aeromonas evaluated using transcriptional analysis and conjectures on disease mechanisms." Cincinnati, Ohio : University of Cincinnati, 2007. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1172346920.

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Thesis (Ph. D.)--University of Cincinnati, 2007.
Title from electronic thesis title page (viewed Apr. 18, 2007). Includes abstract. Keywords: microarrays, transcription changes, virulence, Aeromonas. Includes bibliographical references.

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20

Kauppila, Johanna Heta Katariina [Verfasser], Nils-Göran [Gutachter] Larsson, Aleksandra [Gutachter] Trifunovic, Jan [Gutachter] Riemer, and Jan [Gutachter] Smeitink. "Generating mammalian mitochondrial disease models with mitochondrial DNA mutations / Johanna Heta Katariina Kauppila ; Gutachter: Nils-Göran Larsson, Aleksandra Trifunovic, Jan Riemer, Jan Smeitink." Köln : Universitäts- und Stadtbibliothek Köln, 2018. http://d-nb.info/1165772744/34.

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21

HAYES, SAMUEL Lee. "RESPONSE OF MAMMALIAN MODELS TO EXPOSURE OF BACTERIA FROM THE GENUS AEROMONASEVALUATED USING TRANSCRIPTIONAL ANALYSIS AND CONJECTURES ON DISEASE MECHANISMS." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172346920.

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22

Kade, Ige Joseph. "Interaction of organodiselenides with sulphydryl groups at the active sites of some thiol containing proteins - in vitro and in vivo mechanistic studies in mammalian models of diabetes." Universidade Federal de Santa Maria, 2008. http://repositorio.ufsm.br/handle/1/4398.

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The present study sought to compare the in vitro antioxidant potentials of a newly synthesized organodiselenide, dicholesteroyl diselenide (DCDS) and diphenyl diselenide (DPDS) and their possible interactions with some thiol containing enzymes in different tissues from mammalian system. In addition, the potency of DPDS as antioxidant and antihyperglycaemic agents, and its interaction with thiol containing proteins in various mammalian tissues and organs (hepatic, renal and spleenic and more importantly cerebral tissues) were evaluated in animal models of streptozotocin induced diabetic rats. The in vitro results show that DPDS exhibited a higher glutathione-peroxidase mimetic activity as well as increased ability to oxidize both mono- and di- thiols than DCDS. In addition, while DPDS inhibited thiobarbituric acid reactive substances (TBARS) and protein carbonyls formations in both cerebral and hepatic tissues, induced by either iron (II) or SNP, DCDS exhibited a prooxidant effect in both cerebral and hepatic tissues when iron (II) serves as the prooxidant, However, when TBARS was induced by SNP, DCDS slightly modify TBARS formation in both hepatic and cerebral tissues. Also the activities of cerebral and hepatic delata aminolevulinic acid dehydratase (ð-ALA-D), cerebral Na+/K+- ATPase were significantly inhibited by DPDS and only weakly inhibited by the DCDS. Further studies reveal that the inhibition caused by organodiselenides (in this case, DPDS) on Na+/K+-ATPase activity likely involves the modification of the thiol groups at the ATP binding site of the enzyme. Similarly, different isoforms of lactate dehydrogenase (LDH) were significantly inhibited by both DPDS and DCDS in vitro. Likewise, we observed that the in vitro inhibition of different isoforms of lactate dehydrogenase by DCDS and DPDS likely involves the modification of the -SH groups at the NAD+ binding site of the enzyme. Oral administration of DPDS dissolved in soya bean oil administered to streptozotocin induced diabetes in male albino rats shows that there was significant reduction in blood glucose levels accompanied by a marked reduction of glycated proteins in streptozotocin induced diabetic rats treated with DPDS in relation to untreated streptozotocin induced diabetic. In addition, DPDS was able to significantly ameliorate the levels of Vitamin C and GSH (liver, kidney and spleen), which were decreased in streptozotocin treated rats. Similarly, treatment with DPDS was able to markedly abolish the increase levels of TBARS that were observed in STZ diabetes group. Finally, the inhibition of both ð-ALA-D and some isoforms of LDH caused by hyperglycaemia were prevented by DPDS. We also observed that although streptozotocin evoke a significant diminution on brain s antioxidant status and activity of Na+/K+-ATPase, but the activity of acetylcholineesterase and glutamate uptake and release were not altered. However, DPDS was able to markedly restore the observed imbalance in antioxidant status and sodium pump. Finally, we conclude that organodiselenides are promising antioxidant remedy in the management of diseases caused by oxidative stress. However, their toxicity involves an interaction with thiols on proteins and this study has further demonstrated that the sulphydryl groups in question are critical to the normal function of the protein or enzymes. Most likely, these -SH are associated with thiols at the substrate binding (active site) sites of the enzymes. Interestingly, pharmacological doses of organodiselenides 3mg/kg bw for the study on diabetes do not present any observed toxicity.
O presente estudo quis comparar os potenciais antioxidants in vitro de organoselênios novamente sintetizados, diseleneto dicolesterol e diseleneto de difenila e suas possíveis interações com algumas enzimas contendo tióis em diferentes tecidos de mamíferos. Além disso, o potencial de DPDS como agente antioxidante e antihiperglicêmico, e sua interação com proteínas contendo tióis em vários tecidos e órgãos de mamíferos (hepático, renal, esplênico e, mais importante, tecido cerebral) foram avaliados em modelos animais de streptozotocina induzindo diabetes em ratos. Os resultados in vitro mostram que DPDS exibiu uma maior atividade mimética da glutationa peroxidase bem como aumentada habilidade para oxidar mono e di-tióis que DPDS. Além disso, enquanto o DPDS inibiu substâncias reativas ao ácido tiobarbitpúrico (TBARS) e formação de proteínas carboniladas em tecidos cerebral e hepático, induzidas por ferro(II) ou SNP, DCDS exibiu um efeito pró-oxidante em cérebro e tecido hepático quando ferro(II) serviu como próoxidante, porém, quando TBARS foi induzido por SNP, DCDS modificou a formação de TBARS tanto em tecido cerebral como hepático. Também, as atividades da deltaaminolevulinato desidratase (ð-ALA-D) cerebral e hepática e Na+/K+-ATPase cerebral foram significativamente inibidas por DPDS e somente fracamente inibida por DCDS. Mas estudos revelam que a inibição causada por organodiselenetos (neste caso, DPDS) na atividade da Na+/K+-ATPase envolve a modificação de grupos tiólicos ligados ao sítio ATP da enzima. Similarmente, diferentes isoformas da lactato desidrogenase (LDH) foram significativamente inibidas por DPDS e DCDS in vitro. nós observamos que a inibição in vitro de diferentes isoformas da LDH por DCDS e DPDS envolve a modificação de grupos SH no sítio ligante NAD+ da enzima. a administração oral de DPDS dissolvido em óleo soya administrado a ratos albino machos com diabetes induzida por streptozotocina mostrou que houve uma redução significante nos níveis de glicose sanguínea acompanhada por uma marcada redução nas proteínas glicadas em ratos diabéticos induzidos com streptozitocina tratados com DPDS em relação aos não diabéticos. Além disso, DPDS melhorou significativamente os níveis de vitamina C e GSH (fígado, rim e baço), que foram diminuídos em ratos tratados com streptozotocina. Similarmente, tratamento com DPDS marcadamente aboliu os níveis elevados de TBARS que foram observados no grupo diabético. Finalmente, a inibição da ð-ALA-D e algumas isoformas da LDH causada pela hiperglicemia foram prevenidas por DPDS. Nós também observamos que STZ provocou uma significante diminuição no status antioxidante do cérebro e atividade da Na+/K+- ATPase, mas a atividade da acetilcolinesterase e captação e liberação de glutamato não foram alteradas. Porém, DPDS marcadamente restaurou o desequilíbrio observado no status antioxidante e bomba de sódio. Finalmente, nós concluímos que organoselenetos são remédios antioxidantes promissores no manejo de doenças causadas por estresse oxidativo. Porém, sua toxicidade envolve uma interação com tióis em proteínas e este estudo demonstrou que os grupos sulfidril em questão são críticos para a função normal de enzimas e proteínas. Estes SH são associados com tióis dos sítios de ligação do substrato (sítio ativo) de enzimas. interessantemente, doses farmacológicas de organodiselenetos (3mg/kg para o estudo de diabetes) não apresentou nenhuma toxicidade observada.

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Becker-Weimann, Sabine. "Modeling feedback loops in the mammalian circadian oscillator." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16148.

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In den meisten Organismen tickt eine zirkadiane Uhr mit einer Periode von ungefähr 24 Stunden. Sie ermöglicht ihnen die Zeitmessung ohne äußere Signale. Viele physiologische und zelluläre Prozesse unterliegen zirkadianer Regulation. Die molekulare Uhr besteht aus gekoppelten intrazellulären Rückkopplungen: Die Produkte der Uhrgene regulieren ihre eigene Bildung direkt oder indirekt und erzeugen so molekulare Oszillationen. In dieser Arbeit werden bestehende und neue mathematische Modelle des zirkadianen Oszillators verwendet, um die Bedeutung struktureller Merkmale - insbesondere der Rückkopplungen - für grundlegende zirkadiane Eigenschaften zu untersuchen. In einem Modell (Goodwin-Modell), mit einer negativen Rückkopplung erleichtert sättigende Kinetik in einem Abbauterm, nicht aber in einem Produktionsterm, Oszillationen. Ein neues Modell mit zusätzlicher positiver Rückkopplung erzeugt korrekte Phasen zwischen den Komponenten. Es reproduziert die Phänotypen von zirkadianen Mutanten. Das Modell synchronisiert mit dem Licht/Dunkel-Rhythmus. Die positive Rückkopplung beeinflußt die Robustheit der Oszillationen gegenüber Parametervariationen nur gering. Dies erklärt den rhythmischen Phänotyp von Rev-erb alpha-/- Mäusen, die die positive Rückkopplung nicht besitzen. Die überraschende Wiederherstellung von zirkadianen Oszillationen in der Per2Brdm1/Cry2-/- Doppelmutante kann mit dem Modell erklärt werden. Die Wiederherstellung zirkadianer Oszillationen in der arhythmischen Per2Brdm1 Mutante durch zusätzliche Mutation von Rev-erb alpha-/- wird vorausgesagt. Durch das Einfügen von Rev-erb alpha in das Modell entsteht eine weitere Rückkopplung. Mit diesem neuen Modell koennen Phänotypen von Mutanten reproduziert werden. Zuletzt werden Modelle verschiedener molekularer Oszillatoren und allgemeine Modelle, die aus einer positiven oder negativen Rückkopplung unterschiedlicher Kettenlänge bestehen, bezüglich ihrer Robustheit bei Parametervariationen verglichen. Die strukturelle Anordnung und speziell die Art der Rückkopplung ist wichtig für die Robustheit der Modelle. Die weitere Untersuchung zirkadianer Eigenschaften mit diesen und anderen Modellen wird zum Verständnis der zugrundeliegenden Prinzipien des zirkadianen Oszillators beitragen.
In many organisms the circadian clock ticks with a period of approximately 24 hours, enabling the organisms to keep track of time without any environmental time cues. Many physiological and cellular processes underlie circadian regulation. The molecular clock is a network of intracellular feedback loops: The clock gene products directly or indirectly regulate their own transcription, which results in molecular oscillations. In this thesis, existing and new mathematical models of the circadian oscillator are used to investigate the meaning of structural features - in particular of the feedback loops - for fundamental circadian characteristics. In a simple model (Goodwin model) with one negative feedback loop, saturating kinetics in a degradation term, but not in a production term, support oscillations. A new model containing an additional positive feedback loop shows circadian oscillations with the correct phases between the clock components. The phenotype of several clock mutants can be reproduced. The model synchronizes with the light/dark cycle. Assuming restricted light-input (gating), its phase can be fixed to either light onset or light offset with varying day lengths. In this model, the positive feedback has only a minor influence on the robustness of the circadian oscillations towards parameter variations. This explains the rhythmic phenotype of Rev-erb alpha-/- mutant mice that lack a positive feedback. The model can also explain the unexpected regeneration of circadian oscillations in Per2Brdm1/ Cry2-/- double mutant mice. The regeneration of circadian oscillations in the arrhythmic Per2Brdm1 by additional mutation of Rev-erb alpha is predicted. By including Rev-erb alpha explicitly into the model, another negative feedback loop is added: This model reproduces the phenotypes of several clock mutants. Finally, models describing different molecular oscillators and general models with positive or negative feedback loops of varying chain length are compared with respect to their robustness towards parameter variation. The structural design and in particular the kind of feedback underlying the oscillator seems important for the robustness of the model. Further analysis of circadian features with these and other models will give insight into underlying principles of the circadian oscillator.

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24

ElShamy, Wael M. "Developmental requirements of neurotrophins in the mammalian nervous system /." Stockholm, 1998. http://diss.kib.ki.se/search/module/diss.cfm?19980916elsh.

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25

Humphreys, Robyn. "Using a mouse model to understand the effect of hybridization on skeletal and pelage trait variation in mammalian hybrids." Master's thesis, University of Cape Town, 2018. http://hdl.handle.net/11427/29790.

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Hybridization is thought to have played an important role in human evolution, with hybridizing groups having significant differences in soft tissue trait variation. Ectodermal trait variation is of interest because primate hybrids show increased atypical non-metric dental and cranial trait variation thought to be the result of interactions between parental genomes which have diverged for ectodermal trait development (including hair and tooth development). There were also differences between hybridizing hominin groups for limb measurements which have changed significantly throughout human evolution. Here a mouse model is used to look at the effect of hybridization on coat morphology and long bone length. Using standardized photographs, the differences in mean RGB values for the dorsal and ventral coat were used to determine whether the hybrids were different from their parents for pelage colour of different regions of the body, dorsal ventral colour contrast, and levels of variation in coat colour. The sample is composed of parents from one specific and three sub-specific crosses, as well as F1, F2 and first generation backcrossed (B1) hybrids. Long bone measurements of the forelimbs and hind-limbs were collected from micro-CT scans of the sub-specific F1 hybrids and their parents. Previous data have shown that hybridization can have variable morphological outcomes: hybrids can look like one of the parents, they can be intermediate, or they can have extreme traits outside of the range of variation of the parents. Our results indicate that morphological outcomes for coat colour in F1 hybrids depends on factors such as genetic distance. However, the genetic background of one of the strains used for this experiment might contribute the transgressive phenotype of some of the F1 hybrids. Hybrid morphology also changes in subsequent generations (F2 and B1) as new recombinants formed, with transgressive coat colour phenotypes sometimes appearing even if they are not present in the F1 hybrid groups. Phenotypes produced in F1 hybrids are also seen in subsequent generations of hybrids. All sub-specific F1 hybrids were transgressive for long bone length. Compared to parental groups hybrids have a different relationship between the long bones of the forelimb (ratio of humerus to ulna). This is in line with previous data from primate hybrids, that shows that changes in the relationships between different regions of the body occurs in hybrids producing novel phenotypes. The inter-membral indexes are not significantly different from one of the parents for two of the crosses. This data shows that hybridization can produce novel pelage phenotypes over multiple generations. There were many transitions in hair/skin morphology during human evolution and these tissue groups were and are under a great deal of selective pressure due to their direct interaction with the environment. Thus, understanding how these traits are impacted by hybridization will be important for disentangling how hybridization affected our evolutionary trajectory and ability to occupy new regions of the world. Post cranial data, indicates that F1 hominin hybrids might have longer limbs in relation to parental populations, more work needs to be done on the post cranial remains of posited hominin hybrids as well as pedigreed mammalian hybrids to determine if this is a pattern which can be used to identify hybrids in the fossil record.

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26

Luo, Ching-Hsing. "A dynamic model of the mammalian ventricular action potential: Formulation and physiological simulations." Case Western Reserve University School of Graduate Studies / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1060102425.

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27

Mota, Sílvia Liliana Gomes. "Development of a mammalian cell model to study AIP56." Master's thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/7976.

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Mestrado em Biologia Aplicada - Biologia Molecular e Celular
Fish photobacteriose is a bacterial systemic and deadly infection with rapid course and very high mortalities, caused by the Photobacterium damselae subsp. piscicida (Phdp). Phdp spreads through the bloodstream and secretes the apoptogenic exotoxin AIP56 allowing the pathogen to avoid phagocytosis by inducing the apoptotic death of the host phagocytes. Although AIP56 was found to be a key virulence factor of Phdp and the AIP56-related pathology has been well characterized, the molecular targets of the toxin and the molecular pathways it affects/modulates remain to be disclosed. Recent data revealed that AIP56 is an AB-toxin, possessing an N-terminal metalloprotease domain (A domain) responsible for the catalytic activity of the toxin and a C-terminal domain (B domain) involved in the binding/internalization of the toxin into the cells. The N-terminal domain of AIP56 is homologous to the non-LEE encoded effector C (NleC), a type III secreted effector of enteric pathogenic bacteria that cleaves and inactivates the p65 of NF-kB. However, it remains to be investigated if AIP56 also targets NF-kB p65 and if NF-kB p65 inactivation by AIP56 is linked to the apoptogenic activity of the toxin. So far, AIP56 activity has been being studied using an ex vivo model consisting of freshly isolated sea bass peritoneal leukocytes because although the susceptibility of several mammalian cell lines to AIP56 has been assessed, no apoptosis was observed in any of the cell lines tested. This specificity of the toxin may result from the existence of receptors for AIP56 in phagocytes of susceptible hosts and their absence in mammalian cells and suggests that if AIP56 was able to enter mammalian cells, it would be able to induce apoptosis in those cells. The existence of a mammalian cell model for studying in detail the AIP56 activity would be very advantageous, because there is much more availability of tools to study mammalian cells than sea bass cells. In this work, we tested and optimized different protocols for the intracellular delivery of AIP56 and AIP56-related proteins into HeLa cells. We found that the most efficient methods for intracellular toxin delivery were chemical transfection with toxin-encoding expression vectors and the use of the LF/PA system of Bacillus anthracis. The chemical transfection allows not only to obtain and study transiently transfected cells, but also to develop stable transfected cell lines.
A photobacteriose de peixes é uma infecção sistémica de evolução rápida, causada pela bactéria Gram-negativa Photobacterium damselae subsp. piscicida (Phdp), que provoca elevadas mortalidades em várias espécies de peixes marinhos. Nos animais infectados, a Phdp dissemina-se na corrente sanguínea e secreta a AIP56, uma exotoxina apoptogénica que permite ao agente infeccioso escapar à defesa fagocítica do hospedeiro através da indução da morte por apoptose dos fagócitos. Embora tenha sido demonstrado que a AIP56 é um factor-chave da virulência da Phdp e embora a patologia associada à AIP56 esteja bem caracterizada, os alvos moleculares da toxina e as vias moleculares por ela afectadas continuam por desvendar. Dados recentes revelaram que a AIP56 é uma toxina do tipo AB, contendo um domínio N-terminal (domínio A) de metaloprotease responsável pela actividade catalítica e um domínio C-terminal (domínio B) envolvido na ligação e internalização da toxina pelas células. O domínio N-terminal da AIP56 é homólogo ao non-LEE encoded effector C (NleC), um efector presente em várias bactérias patogénicas entéricas e secretado por um sistema de secreção do tipo III. Foi recentemente descrito que o NleC corta e inactiva o p-65 do NF-kB. Contudo, continua por investigar se a AIP56 também tem como alvo o p-65 do NF-kB e se existe uma relação entre um possível corte do p65 e consequente inactivação do NF-kB e a actividade apoptogénica da toxina. Embora se tenha avaliado a susceptibilidade de várias linhas de celulares de mamíferos à AIP56, pelo facto de não se ter observado a ocorrência de apoptose como consequência da exposição à toxina em nenhuma das linhas testadas, até ao momento, a actividade da AIP56 tem vindo a ser estudada usando um modelo ex vivo que consiste em leucócitos peritoneais isolados de robalo. A especificidade observada poderá resultar do facto de os receptores de membrana para a AIP56 existirem nos fagócitos dos hospedeiros susceptíveis e estarem ausentes nas células de mamífero, sugerindo que se a AIP56 entrasse nas células de mamífero, poderia ser capaz de induzir apoptose dessas células. A existência de um modelo celular de mamífero para estudar os detalhes da actividade da AIP56 seria muito vantajosa, pois permitiria utilizar um vasto leque de ferramentas disponíveis comercialmente que não existem ou não podem ser usadas em estudos com células de robalo. Neste trabalho testamos e optimizamos diferentes protocolos para introduzir a AIP56 e proteínas derivadas da AIP56 em células HeLa. Dos resultados obtidos, conclui-se que os métodos mais eficazes para a introdução da toxina foram a transfecção por método químico e a utilização do sistema LF/PA do Bacillus anthracis. A transfecção química permite não só obter e estudar células transfectadas de forma transiente, mas também desenvolver linhas celulares transfectadas estáveis.

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28

Packer, Hans Levi. "A dominant negative over expression model of mammalian MED12 function." Diss., University of Iowa, 2011. https://ir.uiowa.edu/etd/1051.

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Although schizophrenia has been shown to have a substantial component, there is a paucity of known risk alleles. Furthermore, all of the known risk genes are of small effect sizes. Previously it has been shown that a 12 base pair insertional polymorphism in the in the C-terminal, opposite paired (Opa) domain of the MED12 gene known as MED1212bp represents a small but significant risk for a positive syndrome psychosis. In addition, the MED1212bp polymorphism is found in approximately 1.6 percent of X-chromosomes of northern European decent. Studies in zebrafish show that alterations in MED12 reduces staining for monoaminergic neuronal populations, including dopaminergic and serotonergic populations. However, precise mechanisms through which these changes occur are not known. My goal for this study was to use PC6-3 cells as a mammalian cell culture for studying cellular and transcriptional effects of MED12 in a dopaminergic model system. The approach I took was based on studies that have shown that overexpression of C-terminal proline, glutamine and leucine rich (PQL) and Opa domain constructs interact in a dominant negative manner with several transcriptional regulatory proteins that interact with MED12. GFP tagged PQL and Opa domain constructs were placed into a tetracycline inducible T-REx™ regulated expression vector and introduced into a previously generated PC6-3, TR156 cell line that expresses the Tet-Repressor molecule. In this study, I report a selection bias against stably transfected cell lines strongly expressing constructs containing the two C-terminal PQL-Opa protein domains of MED12. I also show that the described low levels of induction of that construct are associated with small, but significant alterations in nuclear morphology, possibly due to nuclear reorganization. Induction of PQL-Opa domains also increases in cell metabolism as measured by a tetrazolium salt assay, typically associated with increases in proliferation compared to the GFP controls or Opa domain alone. Interestingly, the MTS results in the stable cell lines were not reflected changes in cell numbers from direct cell counts performed by light microscopy, or changes in cell cycle distribution as measured by propidium iodide staining and fluorescence activated cell sorting (FACS). In addition I also show microarray gene expression data for both the stable tetracycline inducible lines, as well as transiently electroporated PC6-3 cells. For both the stable and transient expression experiments, the arrays were characterized by small fold changes, which were not validated by RT-PCR. The stable arrays did not produce any robust findings. However, gene ontology (GO) data, as determined by GoMiner analysis, from the transiently electroporated cells shows that 9 of the top 31 GO categories are related to changes in proliferation and cytoskeletal reorganization. However, despite this trend, the data from the GoMiner analysis was above the level of statistical significance (á = 0.05), as is indicated by the false discovery rates (FDR > 0.3). Analysis of the directionality of expression proved intriguing and demonstrated significant evidence of skewing in the pattern of differential expression of annotated genes where there was a significant tendency for the most significantly differentially expressed probes belonging to 13568 annotated genes to be more highly expressed genes in the electroporated GFP control construct cells than those with the PQL/Opa construct. This is also consistent with a broad overlap of the expression data with ChIP-seq data suggesting that the dominant negative effect may be spread over many MED12 regulated genes, in which case the low expression levels are particularly problematic. While the data from these experiments do not present a clear mechanism for MED12 function, they are informative in developing models of MED12 alteration, and potential improvements are discussed.

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Opuwari, Chinyerum Sylvia. "Effect of tea and herbal infusions on mammalian reproduction and fertility." Thesis, University of the Western Cape, 2013. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_9358_1380809535.

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Camellia sinensis (tea) and Aspalathus linearis (rooibos) may improve reproductive function owing to their antioxidant properties. To test this
hypothesis, male and female rats were given 2% and 5% green tea (Gt), black tea (Bt), unfermented rooibos (Ur) or fermented rooibos (Fr) as sole source of drinking for 52 and 21 days respectively. Control rats received tap water. In addition, TM3 Leydig cells were exposed to 0.025, 0.05, 0.1 and 0.5 % aqueous extracts of green tea, black tea, unfermented and fermented rooibos for 24h. In vitro analysis of tea and the herbal infusion revealed the phenolic property and antioxidant capacity (FRAP) in the order Gt >
Bt >
Ur >
Fr. Camellia sinensis and Aspalathus linearis revealed no significant effect on serum antioxidant capacity (p >
0.05) and lipid peroxidation (MDA) in the kidney or liver in both male and female rats and in the testes of the male rats (p >
0.05). In addition, the antioxidant levels were maintained in the testes, liver and kidneys in both the male and female rats. In the male rats, no significant alterations were observed in body weight gain, liver and reproductive organs weight, and serum testosterone (p >
0.05). Only, 5% green tea significantly increased testosterone level (p <
0.05). Seminiferous tubules displayed complete spermatogenesis with abundant sperm in the lumen in all treated groups. However, a significant decrease in diameter and germinal epithelial height of these tubules were observed (p <
0.05). In the epididymides, epithelial height of caput region showed a significant increase (p <
0.01), while the cauda region was increased by Camellia sinensis but decreased by Aspalathus linearis. Sperm concentration improved significantly by green tea and unfermented rooibos (p <
0.05), while black tea and fermented rooibos produced a non significant effect (p >
0.05). Sperm viability was enhanced in all treatment groups (p <
0.05). Furthermore, green tea, black tea and unfermented rooibos significantly improved the motility of rat sperm (p <
0.05)
fermented rooibos tended to improve it (p >
0.05). In addition, green tea, black tea and fermented rooibos enhanced acrosome reaction (p <
0.05). Creatinine activity was significantly higher in rats treated with black tea, unfermented rooibos or fermented rooibos (p <
0.05), green tea tended to increase it (p >
0.05) reflecting the significant increased kidney weight in the treatment groups at high concentrations. Liver markers, ALT and AST, decreased significantly in all treated groups (p <
0.05), except in 5% fermented rooibos where a significant increase in AST level was observed (p <
0.01). In the female rats, the body weight gain, and reproductive organs weight was no affected (p >
0.05). However, 5% fermented rooibos reduced the ovarian weight (p <
0.05), while 5% unfermented rooibos significantly increased the uterine weight (p <
0.05). Liver weight increased significantly by black tea and unfermented rooibos (p <
0.05) while the kidney weight increased significantly by 5% black tea (p <
0.05). No significant effect was observed in the level of FSH produced, on the other hand, Camellia sinensis significantly lowered the level of LH (p <
0.05), while Aspalathus linearis had no effect (p >
0.05). Creatinine activity was enhanced significantly only by 5% fermented rooibos (p <
0.05). Liver markers, ALT and AST were reduced in most treated groups except in fermented rooibos where an increase was observed. In addition, histological sections revealed no obvious alteration in the ovaries, uteri, kidneys and liver of all treated female rats. Camellia sinensis and Aspalathus linearis significantly reduced the level of testosterone produced in TM3 Leydig cells under stimulated conditions in vitro (p<
0.05). Furthermore, both plants maintained the viability and morphology of the cells. However, at 0.5% of either plant extracts, a significant decrease in the viability (p <
0.05) and altered morphology of the TM3 Leydig cells was observed. In conclusion, Camellia sinensis and Aspalathus linearis significantly improved certain sperm function which might be attributed to their high level of antioxidant activity. However, the prolonged exposure of both plant extracts might result in subtle structural changes in the male reproductive system and impair kidney function. In addition, fermented rooibos at high concentration may also impair the functions of the liver. In vitro, both plants were shown to possess anti-androgenic property on TM3 Leydig cells. Furthermore, both Camellia sinensis and Aspalathus linearis may be classified as weak phytoestrogens due to the changes in the weight of the uterus and ovaries observed.

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30

Elborough, Kieran Michael. "Binding and cleavage of model recombination intermediates by two mammalian proteins." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46289.

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31

Swift, Rachel D. "Understanding the expression and functions of Lrig3 in a mammalian model." Thesis, University of Oxford, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.601125.

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Understanding the transformation of a single-celled fertilized egg to a highlypatterned embryo with three di stinct axes has long been a goal of developmental biology. The Transforming Growth Factor ~ (TGF-~) family of morphogens have essential roles in many developmental patbways. Nodal, a member of this complex and tightly regulated signalling family is responsible for many of the patterning events taking place in the early vertebrate embryo, including germ layer specification and axis determination. Whi lst many components of this signalling pathway have been identified, the precise levels of control indicate other factors or targets still await identification. A Xenopus induction assay using active a member of the TGF-~ family led to up-regulation of Lrig3. Lrig3 is a single~pass transmembrane protein with a structured extracellular domain containing Leucine Rich Repeats and Immunoglobulin·like domains. The in vitro and in vivo expression of the Lrig gene family (Lrigs 1·3) in the developing mouse embryo and postnatal eNS are investigated. A Lrig3 knock-out mouse was created and analysed and bioinfonnatic data on protein structure and func tion was completed. The expression profiles for Lrig J-3 identify distinct differences in expression domains. Significant but not complete overlap exists between LrigJ and 3 which are expressed together in the primitive streak, node, somites and branchial arches. When combined with £he high degree of structural homology these data suggest that Lrigl 9 • I and 3 are able to compensate for each other. Differing expression is observed in me anterior neural crest, branchial arches, portions of the somite tissue and developing limbs. The Lrig3'/o mouse revealed no identifiable phenotype in the developing or adult mouse reinforcing the strong possibi lity of redundancy in the Lrig gene family. A novel low-complexity region was identified in the intracellular domain of the protein. Three-dimensional structural analysis indicated multiple binding sites in the extracellular portion of Lrig3. Expression of Lrig2 and 3 in the central nervous system indicated potential roles for Lrigs in neural plasticity. Future research should focus on identifying interacting partners for Lrig3 and further investigation of its funct ion by breeding LrigJ';o/Lrig3-1o mice . 10

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32

Chen, Hui-Zi. "Mammalian Atypical E2Fs Link Endocycle Control to Cancer." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1316540844.

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33

Pett, Jan Patrick. "Systems level generation of mammalian circadian rhythms and its connection to liver metabolism." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/19960.

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Circadiane Uhren sind endogene Oszillatoren, die 24-Stunden Rhythmen erzeugen. Sie erlauben Organismen deren Physiologie und Verhalten an tägliche Änderungen der Umwelt anzupassen. In Säugetieren basieren solche Uhren auf transkriptional-translationalen Rückkopplungsschleifen, aber es ist noch nicht ganz verstanden, welche Schleifen zur Erzeugung von Rhythmen beitragen. Eine der physiologischen Schlüsselfunktionen von cirkadianen Uhren scheint die zeitliche Anordnung von metabolischen Prozessen zu sein. Im ersten Projekt haben wir eine Methode eingeführt, um systematisch Regulationen in einem datengetriebenen mathematischen Modell der Kernuhr zu testen. Überraschenderweise haben wir ein Rückkopplungsmotif entdeckt, das vorher noch nicht im Zusammenhang mit der circadianen Uhr in Säugetieren in Betracht gezogen wurde. Dieser Repressilator ist mit Gen-knockout Studien und weiteren Perturbationsexperimenten konsistent. Im zweiten Projekt haben wir das Modell wiederholt auf gewebespezifische Datensätze gefitted und essentielle Rückkopplungen in allen Modellversionen identifiziert. Interessanterweise fanden wir dabei für alle gewebespezifischen Datensätze Synergien von Rückkopplungen, die zusammen Rhythmen erzeugen. Desweiteren haben wir festgestellt, dass die Synergien sich abhängig vom Gewebe unterscheiden. Im dritten Projekt haben wir die circadianen Aspekte des Metabolismus untersucht. Wir haben circadiane Komponenten in verschiedenen omics Studien identifiziert, integriert und auf ein metabolisches Netzwerk gemapped. Unsere Analyse hat bestätigt, dass viele Stoffwechselwege vermutlich circadianen Rhythmen folgen. Interessanterweise haben wir festgestellt, dass die durchschnittlichen Phasen von rhythmischen Komponenten sich zwischen verschiedenen Stoffwechselwegen unterscheiden. Solche Unterschiede könnten eine zeitliche Anpassung metabolischer Funktionen an Zeiten darstellen zu denen sie gebraucht werden.
Circadian clocks are endogenous oscillators that generate 24-hour rhythms. They allow many organisms to synchronize their physiology and behaviour with daily changes of the environment. In mammals such clocks are based on transcriptional-translational feedback loops, however, it is not fully understood which feedback loops contribute to rhythm generation. Within an organism different clocks are distinguished by their localization in different organs. One of the key physiological functions of circadian clocks in various organs seems to be the temporal alignment of metabolic processes. In the first project we introduced and applied a method to systematically test regulations in a data-driven mathematical model of the core clock. Surprisingly, we discovered a feedback loop that has previously not been considered in the context of the mammalian circadian clock. This repressilator is consistent with knockout studies and further perturbation experiments. It could constitute an explanation for different phases observed between Cryptochromes, which are part of the core clock. In the second project we repeatedly fitted the same mathematical model to tissue-specific data sets and identified essential feedback loops in all model versions. Interestingly, for all tissue-specific data sets we found synergies of loops generating rhythms together. Further, we found that the synergies differ depending on the tissue. In the third project we examined the circadian aspects of metabolism. We identified rhythmic data in different omics studies, integrated and mapped them to a metabolic network. Our analysis confirmed that many metabolic pathways may follow circadian rhythms. Interestingly, we also found that the average peak times of rhythmic components between various pathways differ. Such differences might reflect a temporal alignment of metabolic functions to the time when they are required.

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34

Tsang, Hiu-Gwen. "Investigating gene expression patterns in the mammalian cardiovascular system." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31180.

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The cardiovascular system is an essential component of mammalian biology. It is a complex network of various tissues and structures with unique functions. The function of the cardiovascular system is to supply nutrients including oxygen to the various cells, tissues and organs within the body, and remove waste products from them. Given the importance of this role, it is not surprising that there are countless regulatory mechanisms at the molecular, cellular and tissue levels that are required to support this functional system. Perturbations in parts of this system are likely to lead to abnormalities, and thus give rise to cardiovascular-related diseases. Despite the currently expanding list of genes reported to be involved in a variety of cardiovascular-related diseases, including calcific aortic valve disease (CAVD), the functions and associated pathways of these factors in both normal and pathological physiology have yet to be fully understood, such as at the transcriptomic level. In this thesis, a genome-wide transcriptomic atlas of the healthy mammalian cardiovascular system was generated using the sheep as a large animal model. This atlas was generated using RNA-seq, with the aim of further understanding normal gene expression patterns in the context of the known physiology of healthy mammalian tissues. Through this work, I identified novel gene networks and detailed functional clustering of co-expressed genes with region-specific expression and specialised cardiovascular roles. One interesting cluster was highly expressed in the cardiac valves, and shared genes found in physiological bone development, such as bone morphogenetic protein 4 (BMP4), collagen type I alpha 2 (COL1A2), Sry homeobox 8 (SOX8) and bone gamma-carboxyglutamate protein (BGLAP), some of which have been implicated in vascular calcification. Further to this work, I studied the expression profiles of these key cardiovascular genes during development in the sheep from foetal to adult stages. In addition, I investigated the gene expression patterns of various key vascular calcification genes. These studies showed differential expression of genes in the different cardiovascular tissues, demonstrating transcriptional differences between these different tissues known to have different functions. CAVD involves progressive valve leaflet thickening and severe calcification, resulting in impaired leaflet motion. The in vitro calcification of primary rat, human, porcine and bovine aortic valve interstitial cells (VICs) is commonly employed to examine the mechanisms of CAVD. However, to date, no published studies have utilised cell lines to investigate this process Thus, in this project, I generated and evaluated the calcification potential of an immortalised cell line derived from sheep aortic VICs (SAVICs). This novel large animal in vitro model of CAVD was demonstrated to calcify under high calcium and phosphate conditions. Changes in the expression of key calcification genes during VIC calcification was also observed, including increased mRNA expression of bone markers Runt-related transcription factor 2 (RUNX2) and sodium-dependent phosphate transporter 1 (PiT1), and a concomitant decrease in matrix Gla protein (MGP) mRNA expression. In addition, the role of extracellular nucleotides and their receptors (P2 receptors), which have been previously shown to be important in bone and vascular calcification, were investigated using SAVICs in vitro. This study has shown that extracellular nucleotides, particularly adenosine 5’-triphosphate (ATP) and uridine 5’-triphosphate (UTP) and other agonists of P2 receptors, reduced VIC calcification in vitro. Moreover, the cutting-edge gene-editing technology, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9), was successfully applied to generate large animal models of cardiovascular-related diseases. In this project, I applied the CRISPR/Cas9 technology to edit ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and fibrillin 1 (FBN1) to generate two models of vascular calcification and Marfan Syndrome (MFS), respectively. In the ENPP1-edited animals, soft tissue calcification has been observed in the biallelic mutant and homozygous pigs. In this project, I have developed a range of novel in vitro and in vivo tools to advance the study of cardiovascular disease. These studies demonstrate that large animal models are highly valuable in the field of cardiovascular biology. The in vivo and in vitro experimental models described should facilitate detailed analysis of cardiovascular molecular biology and ultimately lead to therapies which will minimise the morbidity and mortality currently arising from cardiovascular pathology.

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Aitken, Sarah Jane. "The pathological and genomic impact of CTCF depletion in mammalian model systems." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/284403.

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CCCTC-binding factor (CTCF) binds DNA, thereby helping to partition the mammalian genome into discrete structural and regulatory domains. In doing so, it insulates chromatin and fine-tunes gene activation, repression, and silencing. Complete removal of CTCF from mammalian cells causes catastrophic genomic dysregulation, most likely due to widespread collapse of 3D chromatin looping within the nucleus. In contrast, Ctcf hemizygous mice with lifelong reduction in CTCF expression are viable but have an increased incidence of spontaneous multi-lineage malignancies. In addition, CTCF is mutated in many human cancers and is thus implicated as a tumour suppressor gene. This study aimed to interrogate the genome-wide consequences of a reduced genomic concentration of Ctcf and its implications for carcinogenesis. In a genetically engineered mouse model, Ctcf hemizygous cells showed modest but robust changes in almost a thousand sites of genomic CTCF occupancy; these were enriched for lower affinity binding events with weaker evolutionary conservation across the mouse lineage. Furthermore, several hundred genes concentrated in cancer-related pathways were dysregulated due to changes in transcriptional regulation. Global chromatin structure was preserved but some loop interactions were destabilised, often around differentially expressed genes and their enhancers. Importantly, these transcriptional alterations were also seen in human cancers. These findings were then examined in a hepatocyte-specific mouse model of Ctcf hemizygosity with diethylnitrosamine-induced liver tumours. Ctcf hemizygous mice had a subtle liver-specific phenotype, although the overall tumour burden in Ctcf hemizygous and wild-type mice was the same. Using whole genome sequencing, the highly reproducible mutational signature caused by DEN exposure was characterised, revealing that Braf(V637E), orthologous to BRAF(V600E) in humans, was the predominant oncogenic driver in these liver tumours. Taken together, while Ctcf loss is partially physiologically compensated, chronic CTCF depletion dysregulates gene expression by subtly altering transcriptional regulation. This study also represents the first comprehensive genome-wide and histopathological characterisation of this commonly used liver cancer model.

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Harrison, Sarah Ellys. "Utilising embryonic and extra-embryonic stem cells to model early mammalian embryogenesis in vitro." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/275424.

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Successful mammalian development to term requires that embryonic and extra-embryonic tissues communicate and grow in coordination, to form the body. After implanting into the uterus, the mouse embryo is comprised of three cell lineages: first, the embryonic epiblast (EPI) that forms the embryo proper, second, the extra-embryonic ectoderm (ExE) which contributes to the foetal portion of the placenta, and third, the visceral endoderm (VE) that contributes to the yolk sac. These three tissues form a characteristic ‘egg-cylinder’ structure, which allows signals to be exchanged between them and sets the stage for body axis establishment and subsequent tissue patterning. The mechanisms underlying this process are difficult to study in vivo because a different genetically manipulated mouse line must be generated to investigate each factor involved. This difficulty has prompted efforts to model mammalian embryogenesis in vitro, using cell lines, which are more amenable to genetic manipulation. The pluripotent state of the EPI can be captured in vitro as mammalian embryonic stem cells (ESCs). Although mouse ESCs have been shown to contribute to all adult tissues in chimeric embryos, they cannot undertake embryogenesis when allowed to differentiate in culture. Previous studies have shown that ESCs formed into three-dimensional (3D) aggregates, called embryoid bodies, can become patterned and express genes associated with early tissue differentiation. However, embryoid bodies cannot recapitulate embryonic architecture and therefore may not accurately reflect what happens in the embryo. In this study, a new technique was developed to model early mouse development which is more faithful to the embryo. ESCs were co-cultured with stem cells derived from the ExE, termed trophoblast stem cells (TSCs), embedded within extracellular matrix (ECM). These culture conditions lead to the self-assembly of embryo-like structures with similar architecture to the mouse egg cylinder. They were comprised of an embryonic compartment derived from ESCs abutting an extra-embryonic compartment derived from TSCs, and hence were named ‘ETS-embryos’. These structures developed a continuous cavity at their centre, which formed via a similar sequence of events to those that lead to pro-amniotic cavity formation in the mouse embryo, and required active Nodal/Activin signalling. After cavitation, ‘ETS-embryos’ developed regionalised mesodermal tissue and primordial germ cell-like cells originating at the boundary between embryonic and extra-embryonic compartments. Inhibitor studies revealed that this occurred in response to endogenous Wnt and BMP signalling, pathways which also govern these tissue specification events in the early mouse embryo. To demonstrate that ‘ETS-embryos’ were comparable to mouse embryos at the global transcriptional level, RNA-sequencing was then performed on different tissue regions of ‘ETS-embryos’ and the resulting transcriptomes were compared to datasets from mouse embryos. These data showed that ‘ETS-embryos’ were highly similar to mouse embryos at post-implantation stages in their overall gene expression patterns. Taken together, these results indicate that ‘ETS-embryos’ are an accurate in vitro model of mammalian embryogenesis, which can be used to complement studies undertaken in vivo to investigate early development.

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Avva, Jayant. "Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781.

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Patterson, Sean Ingram. "Action of neuroinflammatory mediators on a cell line model for mammalian sensory neurones." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304412.

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Bussek, Alexandra, Erich Wettwer, Torsten Christ, Horst Lohmann, Patrizia Camelliti, and Ursula Ravens. "Tissue Slices from Adult Mammalian Hearts as a Model for Pharmacological Drug Testing." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-137634.

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Aim: Isolated papillary muscles and enzymatically dissociated myocytes of guinea-pig hearts are routinely used for experimental cardiac research. The aim of our study is to investigate adult mammalian ventricular slices as an alternative preparation. Method: Vibratome cut ventricular slices (350 μm thick) were examined histologically and with 2-photon microscopy for fibre orientation. Intracellular action potentials were recorded with conventional glass microelectrodes, extracellular potentials were measured with tungsten platinum electrodes and multi-electrode arrays (MEA). Results: Dominant direction of fibre orientation was absent in vertical and horizontal transmural slices, but was longitudinal in tangential slices. Control action potential duration (APD90, 169.9 ± 4 ms) and drug effects on this parameter were similar to papillary muscles. The L-type Ca-channel blocker nifedipine shortened APD90 with a half maximal effective concentration (EC50) of 4.5 μM. The IKr blocker E4031 and neuroleptic drug risperidone prolonged APD90 with EC50 values of 31 nM and 0.67 μM, respectively. Mapping field potentials on multi-electrode arrays showed uniform spread of excitation with a mean conduction velocity of 0.47 m ⋅ s-1. Conclusion: Slices from adult mammalian hearts could become a useful routine model for electrophysiological and pharmacological research
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

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Bussek, Alexandra, Erich Wettwer, Torsten Christ, Horst Lohmann, Patrizia Camelliti, and Ursula Ravens. "Tissue Slices from Adult Mammalian Hearts as a Model for Pharmacological Drug Testing." Karger, 2009. https://tud.qucosa.de/id/qucosa%3A27744.

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Aim: Isolated papillary muscles and enzymatically dissociated myocytes of guinea-pig hearts are routinely used for experimental cardiac research. The aim of our study is to investigate adult mammalian ventricular slices as an alternative preparation. Method: Vibratome cut ventricular slices (350 μm thick) were examined histologically and with 2-photon microscopy for fibre orientation. Intracellular action potentials were recorded with conventional glass microelectrodes, extracellular potentials were measured with tungsten platinum electrodes and multi-electrode arrays (MEA). Results: Dominant direction of fibre orientation was absent in vertical and horizontal transmural slices, but was longitudinal in tangential slices. Control action potential duration (APD90, 169.9 ± 4 ms) and drug effects on this parameter were similar to papillary muscles. The L-type Ca-channel blocker nifedipine shortened APD90 with a half maximal effective concentration (EC50) of 4.5 μM. The IKr blocker E4031 and neuroleptic drug risperidone prolonged APD90 with EC50 values of 31 nM and 0.67 μM, respectively. Mapping field potentials on multi-electrode arrays showed uniform spread of excitation with a mean conduction velocity of 0.47 m ⋅ s-1. Conclusion: Slices from adult mammalian hearts could become a useful routine model for electrophysiological and pharmacological research.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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41

Cai, Jingfei. "Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C." Thesis, Boston College, 2013. http://hdl.handle.net/2345/3872.

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Thesis advisor: Mary F. Roberts
Thesis advisor: Eranthie Weerapana
Peripheral proteins from mammals often exhibit multi-domain structures and require metal ions such as calcium as co-factors. This dissertation investigates two types of such proteins -- pulmonary collectins (surfactant proteins A and D) and phosphatidylinositol-specific phospholipase C (PLC) delta1 -- and their interactions with model membranes. One approach to work around the complexity brought upon by such multi-domain protein structure is to use a truncated construct or an isolated single domain. For pulmonary collectins, homotrimers consisting of the neck domain and the carbohydrate recognition domain were used in a novel NMR assay for better understanding of their lipid-specific interactions with the membranes. For PLC delta1, we were particularly interested in the role of the EF-hand domain. The isolated EF-hand domain of PLC delta1 was first used to characterize its interactions with membranes and identify key residues responsible for such interactions. These key residues in the N terminal lobe of the EF-hand domain, either cationic or hydrophobic, were then found to affect the hydrolysis activity of the full-length enzyme. A common role for this region of the PLC in facilitating proper membrane association was thus proposed
Thesis (PhD) — Boston College, 2013
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry

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42

Singh, Geetanjali. "Analysis of genetic mutations using a recombinant model of the mammalian pyruvate dehydrogenase complex." Thesis, Thesis restricted. Connect to e-thesis to view abstract, 2008. http://theses.gla.ac.uk/214/.

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Thesis (Ph.D.) - University of Glasgow, 2008.
Ph.D. thesis submitted to the Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, 2008. Includes bibliographical references. Print version also available.

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Sidoli, Fabio. "Systematic development of a coupled population-balance-single-cell model for mammalian cell cultures." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.428151.

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Mgwebi, Thandiswa. "Morphological investigations into the development of the mammalian corneal endothelium using the mouse model." Doctoral thesis, University of Cape Town, 2004. http://hdl.handle.net/11427/3268.

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Includes bibliographical references (leaves 83-89).
The corneal endothelium (CE), a mesenchyme-derived tissue, is a monolayer of squamous cells on the inner corneal surface. In Foxc1-1• mice, the CE fails to form. The understanding of the cause of this defect has implications for the study of human eye disorders that are related to FOXC1 mutations. To understand the basis of CE defects in Foxc1-1- mice, an analysis of normal CE development was performed using scanning electron microscopy. Results showed that in normal mice the transformation from mesenchyme to endothelium was initiated at embryonic day (E) 12.5 and was characterised by a change from stellate to cobblestone shape and the formation of junctions. In FoxcN- mice, the process was initiated but a cobblestone shape not attained. The expression of adherens (N-cadherin) and tight junction (Z0-1) proteins was investigated by immunoflouresence microscopy. In the normal embryo, the expression of N-cadherin was initially in cytoplasmic vesicles and later at the cell membranes. ZO-l was first detected at the cell peripheries at E13.5. In Foxct-I- mice, N-cadherin peripheral bands failed to form. ZO-l was not expressed. These results suggest that the failure to form a monolayered CE in Foxc1 mice is due to incomplete mesenchyme-endothelial conversion. Junction formation was further investigated in vitro. N-cadherin was cytoplasmic in pre-confluent cells and at cell edges in confluent cells. ZO-l was not detected. These results suggest that in vitro, these cells are either unable to form tight junctions or the culture medium does not contain the appropriate signalling molecules.

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Sankaran, Saumya M. "A functional analysis of the mammalian E3 ubiquitin ligase WWP1 in a yeast model." Waltham, Mass. : Brandeis University, 2009. http://dcoll.brandeis.edu/handle/10192/23252.

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Conzelmann, Holger. "Mathematical modeling of biochemical signal transduction pathways in mammalian cells a domain-oriented approach to reduce combinatorial complexity /." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-38819.

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Kabir, Mitra. "Prediction of mammalian essential genes based on sequence and functional features." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/prediction-of-mammalian-essential-genes-based-on-sequence-and-functional-features(cf8eeed5-c2b3-47c3-9a8f-2cc290c90d56).html.

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Essential genes are those whose presence is imperative for an organism's survival, whereas the functions of non-essential genes may be useful but not critical. Abnormal functionality of essential genes may lead to defects or death at an early stage of life. Knowledge of essential genes is therefore key to understanding development, maintenance of major cellular processes and tissue-specific functions that are crucial for life. Existing experimental techniques for identifying essential genes are accurate, but most of them are time consuming and expensive. Predicting essential genes using computational methods, therefore, would be of great value as they circumvent experimental constraints. Our research is based on the hypothesis that mammalian essential (lethal) and non-essential (viable) genes are distinguishable by various properties. We examined a wide range of features of Mus musculus genes, including sequence, protein-protein interactions, gene expression and function, and found 75 features that were statistically discriminative between lethal and viable genes. These features were used as inputs to create a novel machine learning classifier, allowing the prediction of a mouse gene as lethal or viable with the cross-validation and blind test accuracies of ∼91% and ∼93%, respectively. The prediction results are promising, indicating that our classifier is an effective mammalian essential gene prediction method. We further developed the mouse gene essentiality study by analysing the association between essentiality and gene duplication. Mouse genes were labelled as singletons or duplicates, and their expression patterns over 13 developmental stages were examined. We found that lethal genes originating from duplicates are considerably lower in proportion than singletons. At all developmental stages a significantly higher proportion of singletons and lethal genes are expressed than duplicates and viable genes. Lethal genes were also found to be more ancient than viable genes. In addition, we observed that duplicate pairs with similar patterns of developmental co-expression are more likely to be viable; lethal gene duplicate pairs do not have such a trend. Overall, these results suggest that duplicate genes in mouse are less likely to be essential than singletons. Finally, we investigated the evolutionary age of mouse genes across development to see if the morphological hourglass pattern exists in the mouse. We found that in mouse embryos, genes expressed in early and late stages are evolutionarily younger than those expressed in mid-embryogenesis, thus yielding an hourglass pattern. However, the oldest genes are not expressed at the phylotypic stage stated in prior studies, but instead at an earlier time point - the egg cylinder stage. These results question the application of the hourglass model to mouse development.

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Maree, Liana. "Sperm mitochondria: Species specificity and relationships to sperm morphometric features and sperm function in selected mammalian species." Thesis, University of the Western Cape, 2011. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_1728_1363788268.

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Numerous studies on mammalian spermatozoa have reported large variations in the dimensions of the main sperm structural components, namely the head, midpiece and flagellum. These variations in sperm architecture are believed to be adaptations for functioning of spermatozoa in complex environments outside the male reproductive system. The midpiece of the mammalian
permatozoon contains a varied number of mitochondria, but the reason for the marked difference in the size and structure of this sperm component is not clear. This study
confirmed the variations in the sperm morphometry of seven selected mammalian species and revealed unique features of the sperm midpiece and sperm mitochondria of these seven species. Evaluation of several sperm kinematic parameters revealed the unique swimming characteristics of the different spermatozoa. The importance of using standardized motility
parameters was highlighted as well as the assessment of different subpopulations of spermatozoa in order to produce more reliable and comparable data. Investigating the role of sperm mitochondria in human sperm
metabolism indicated that these organelles are related to sperm function in terms of sperm motility. Furthermore, it was suggested that glycolysis and mitochondrial respiration are linked processes and that both are important for the maintenance of human sperm motility. By optimizing and employing standardized experimental procedures and analysis techniques, this study was
able to confirm the species specificity of almost all the sperm parameters evaluated, while also elucidating the phylogenetic relatedness of the non-human primate species. In conclusion, the present study has confirmed that the various midpiece morphometry parameters are related to the remaining sperm morphometry parameters as well as to the sperm kinematic parameters.
These proposed associations between the various sperm parameters were used to explain the sperm velocity of two hypothetical and morphologically different sperm structures. Therefore, the results of the current study support the idea of co-evolution between sperm components in mammalian spermatozoa and propose that the midpiece morphometry parameters that are selected for in these spermatozoa are midpiece volume, total number of mitochondrial gyres, thickness of the mitochondrial sheath and mitochondrial height.

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Hanon, Elodie. "A novel model of action for TSH (thyrotropin stimulating hormone) in the mammalian neuroendocrine system." Thesis, Available from the University of Aberdeen Library and Historic Collections Digital Resources, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?application=DIGITOOL-3&owner=resourcediscovery&custom_att_2=simple_viewer&pid=53386.

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Permana, Paskasari A. "SV40 minichromosome: A mammalian replicon model for investigations of antineoplastic drugs and DNA damaging agents /." The Ohio State University, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487846885776862.

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Dissertations / Theses on the topic 'Mammalian models'

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