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1
Lynn, C. "Using adaptation to uncover motion processing mechanisms." Thesis, Queen's University Belfast, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546383.
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von, Mackensen Jana. "Thinking Friction : Uncover the true colours of Berlin." Thesis, KTH, Stadsbyggnad, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-100151.
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Utsunomiya, Yuri Tani [UNESP]. "Genome-wide scans to uncover loci underlying bovine reproductive biology." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/98165.
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000748821.pdf: 4613414 bytes, checksum: 5df263a22daac5758702e6a97e66c980 (MD5)O desempenho reprodutivo dos animais tem um grande impacto sobre a indústria da carne bovina. A caracterização de regiões genômicas que afetam a fertilidade dos animais pode contribuir para a identificação de marcadores preditivos de desempenho reprodutivo e desvendar os mecanismos moleculares envolvidos em aspectos complexos da biologia reprodutiva dos bovinos. Nos dois primeiros estudos relatados, os genomas de touros da raça Nelore (Bos indicus) foram examinados em busca de loci que explicam variação nas características peso ao nascer (PN) e perímetro escrotal (PE), utilizando dados de mais de 777.000 marcadores do tipo polimorfismo de sítio único (single nucleotide polymorphism - SNP). Um segmento do cromossomo 14, o qual engloba o gene ortólogo PLAG1 que afeta estatura em humanos, foi encontrado tanto em PN quanto em PE. Este locus possui efeitos pleiotrópicos sobre características reprodutivas e de tamanho corporal em bovinos, e representa um ponto de partida para a dissecção da genética da fertilidade bovina. Em outro estudo, um teste estatístico composto foi desenvolvido e aplicado na busca de evidências de assinaturas de seleção no genoma de raças bovinas de leite e de corte. Padrões de variação genética que podem ter sido moldadas pela seleção humana foram detectados no genoma de quatro diferentes raças bovinas (Angus, Pardo Suíço, Gir e Nelore). O estudo indica o gene Cornichon 3 (CNIH3) como um forte candidato, que pode estar envolvido na regulação do pico pré-ovulatório do hormônio luteinizante na raça Pardo-Suíço. Embora estes resultados apenas toquem a superfície dos mecanismos moleculares por trás da reprodução dos bovinos, os loci aqui identificados abrigam novos e conhecidos genes candidatos que afetam a fertilidade da espécie, e oferecem novas perspectivas sobre aspectos complexos de sua biologia reprodutiva
Reproductive performance has a high impact on the beef cattle industry. The characterization of genomic regions affecting fertility can contribute to the identification of diagnostic markers for reproductive performance and uncover molecular mechanisms underlying complex aspects of bovine reproductive biology. In the first two reported studies, the genomes of progeny-tested Nellore bulls (Bos indicus) were scanned for loci explaining variance in birth weight (BW) and scrotal circunferemce (SC), using data containing over 777,000 single nucleotide polymorphism (SNP) markers. Among the identified loci, a chromosome segment located on autosome 14, encompassing the orthologous human stature gene pleiomorphic adenoma 1 (PLAG1), was found to affect both BW and SC. This locus has been found to have pleiotropic effects on reproduction and body size traits in cattle, and represents a starting point to the dissection of the complex inheritance of bovine fertility. In a separate study, a composite statistical test was developed and applied to scan dairy and beef cattle genomes for evidences of natural and artificial selection signatures. Patterns of genetic variation that may have been shaped by human-driven selection were detected in the genomes of four different cattle breeds (Angus, Brown Swiss, Gyr and Nellore). The study pointed to the Cornichon homolog 3 gene (CNIH3) as a strong candidate involved in the regulation of pre-ovulatory luteinizing hormone surge in Brown Swiss. Although these findings only scratch the surface of the molecular mechanisms underlying bovine reproduction, the loci identified here harbor known and novel functional candidate genes affecting fertility in cattle and offer new insights on complex aspects of bovine reproductive biology
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Ashwanden, Cordelia. "An ethnographic journey to uncover the culture of dialysis units." Thesis, University of Southampton, 2002. https://eprints.soton.ac.uk/50616/.
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A major challenge of the 21st century for the health-care professionals is to provide care for the ever-expanding population of people with renal-failure. Patient numbers are rising and specialist nurses, who are the pivotal factor in haemodialysis units, are becoming increasingly scarce. In this context it has become essential to understand the dynamics and functioning of haemodialysis units. The aim of this research project is to increase understanding of the lives of patients and carers by uncovering the culture of haemodialysis units. Ethnography, from the naturalistic paradigm, is a holistic study of culture, developed out of classical philosophy. This study examines the entire social world of the dialysis unit. It describes the ethnographic journey made over twenty-four months' research in two different dialysis units. The participants were amongst patients and carers from these two units. The fieldwork, which facilitated data collection, was based on a participatory process of observation, interviews and participant feedback. These data were analysed into domains and themes using Spradley's Research development sequence (1980) and the reflexive process. Through the theme-based analysis used during the research and writing of this ethnographic study an emergent theory of partnership in care became apparent. Such a theory contributes to our understanding of the culture of the dialysis unit. Uncovering the culture of dialysis units will not prevent the increase in numbers of people needing Renal Replacement Therapy. It does, however, shed light on the condition of living with renal failure and the nature of partnerships developed in the haemodialysis unit. It is these partnerships between people, machines and the environment that sets the dialysis unit apart in the hospital, giving it its own particular culture. Partnership means shared care where patients and carers work towards mutual goals. The realisation of these common goals leads towards the overall objective of better treatment outcomes.
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Utsunomiya, Yuri Tani. "Genome-wide scans to uncover loci underlying bovine reproductive biology /." Jaboticabal, 2013. http://hdl.handle.net/11449/98165.
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Orientador: José Fernando GarciaCoorientador: Johann Sölkner
Banca: Joaquim Mansano Garcia
Banca: Adriana Santana do Carmo
Resumo: O desempenho reprodutivo dos animais tem um grande impacto sobre a indústria da carne bovina. A caracterização de regiões genômicas que afetam a fertilidade dos animais pode contribuir para a identificação de marcadores preditivos de desempenho reprodutivo e desvendar os mecanismos moleculares envolvidos em aspectos complexos da biologia reprodutiva dos bovinos. Nos dois primeiros estudos relatados, os genomas de touros da raça Nelore (Bos indicus) foram examinados em busca de loci que explicam variação nas características peso ao nascer (PN) e perímetro escrotal (PE), utilizando dados de mais de 777.000 marcadores do tipo polimorfismo de sítio único (single nucleotide polymorphism - SNP). Um segmento do cromossomo 14, o qual engloba o gene ortólogo PLAG1 que afeta estatura em humanos, foi encontrado tanto em PN quanto em PE. Este locus possui efeitos pleiotrópicos sobre características reprodutivas e de tamanho corporal em bovinos, e representa um ponto de partida para a dissecção da genética da fertilidade bovina. Em outro estudo, um teste estatístico composto foi desenvolvido e aplicado na busca de evidências de assinaturas de seleção no genoma de raças bovinas de leite e de corte. Padrões de variação genética que podem ter sido moldadas pela seleção humana foram detectados no genoma de quatro diferentes raças bovinas (Angus, Pardo Suíço, Gir e Nelore). O estudo indica o gene Cornichon 3 (CNIH3) como um forte candidato, que pode estar envolvido na regulação do pico pré-ovulatório do hormônio luteinizante na raça Pardo-Suíço. Embora estes resultados apenas toquem a superfície dos mecanismos moleculares por trás da reprodução dos bovinos, os loci aqui identificados abrigam novos e conhecidos genes candidatos que afetam a fertilidade da espécie, e oferecem novas perspectivas sobre aspectos complexos de sua biologia reprodutiva
Abstract: Reproductive performance has a high impact on the beef cattle industry. The characterization of genomic regions affecting fertility can contribute to the identification of diagnostic markers for reproductive performance and uncover molecular mechanisms underlying complex aspects of bovine reproductive biology. In the first two reported studies, the genomes of progeny-tested Nellore bulls (Bos indicus) were scanned for loci explaining variance in birth weight (BW) and scrotal circunferemce (SC), using data containing over 777,000 single nucleotide polymorphism (SNP) markers. Among the identified loci, a chromosome segment located on autosome 14, encompassing the orthologous human stature gene pleiomorphic adenoma 1 (PLAG1), was found to affect both BW and SC. This locus has been found to have pleiotropic effects on reproduction and body size traits in cattle, and represents a starting point to the dissection of the complex inheritance of bovine fertility. In a separate study, a composite statistical test was developed and applied to scan dairy and beef cattle genomes for evidences of natural and artificial selection signatures. Patterns of genetic variation that may have been shaped by human-driven selection were detected in the genomes of four different cattle breeds (Angus, Brown Swiss, Gyr and Nellore). The study pointed to the Cornichon homolog 3 gene (CNIH3) as a strong candidate involved in the regulation of pre-ovulatory luteinizing hormone surge in Brown Swiss. Although these findings only scratch the surface of the molecular mechanisms underlying bovine reproduction, the loci identified here harbor known and novel functional candidate genes affecting fertility in cattle and offer new insights on complex aspects of bovine reproductive biology
Mestre
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Shires, Katherine L. "Using IEG's to uncover pathways for spatial learning in the rat." Thesis, Cardiff University, 2006. http://orca.cf.ac.uk/54312/.
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This thesis concentrates on the induction of the immediate early genes zif268 and c-fos in a functional and dysfunctional brain network. Initial studies focused on the creation of a task to allow the study of immediate early gene activation after working memory. Previous studies using such a paradigm have compared the animals performing the experimental task with poorly matched control groups. Experiments in this thesis attempted to rectify this. A group of experiments using the water maze found decreases in Zif268 activation in the experimental group as compared to control groups, mainly in the hippocampus and some parahippocampal areas. This was believed to have arisen because of a streamlining of the brain network in the Working Memory group. An increase in c-Fos immunoreactivity was seen in the Working Memory group as compared to controls in prefrontal regions. Structural equation modelling analysis was performed, which allows immediate early gene counts to be used to analyse networks of brain regions. In the Working Memory group connections were seen between the parahippocampal regions and the subiculum that progressed via the hippocampus, indicating that the hippocampus was still engaged by the task. In the control group analysed no such hippocampal pathway was found. This water maze task was then used to study zif268-EGFP activation in a novel transgenic rodent model, where the Zif268 promoter drives the expression of a fluorescent protein EGFP. Activation of both EGFP and Zif268 immunoreactivity was seen in the CA1 region of the animals performing the control task. No EGFP activation was seen in this region in the Working Memory group even though EGFP expression was seen in other regions. The GFP protein was also able to be seen under direct visualisation in the CA1 and dentate gyrus region of control animals. Concerning the dysfunctional brain, gene expression was analysed in the retrosplenial cortex after NMDA lesions of the anterior thalamic nuclei. Previous research has shown that lesions produce a dramatic hypoactivity in the protein products of the immediate early genes c-fos and zif268. Microarray analysis of retrosplenial tissue revealed that as well as decreases in expression of genes related to repair and cell adhesion/neurogenesis, an increase in c-fos mRNA was seen in the lesion hemisphere of the brain. This pattern of expression is opposite to that of the protein. Possible reasons for this are discussed.
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Rogers, Robert. "Capturing moments : an investigation into how best to uncover teachers' knowledge." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365018.
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Proudfoot, Jeffrey Gainer. "Identifying Deception Using Novel Technology-Based Approaches to Uncover Concealed Information." Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/316781.
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Concealing information, one of the many forms of deception, is a pervasive phenomenon as it is present in virtually every facet of interpersonal communication. In some cases, information concealment can have profound implications (e.g., insider threats in organizations, security screening at the border, and criminal interviews). New technologies are under development to aid in identifying concealed information, however, additional research is needed in three key areas to increase the feasibility of using these technologies in real-world credibility assessment contexts. First, research is needed to investigate the accuracy of new credibility assessment technologies relative to existing deception-detection systems. Demonstrating that new technologies meet or exceed detection accuracies of existing systems (e.g., the polygraph) is critical. Second, research is needed to determine if a targetless Concealed Information Test (CIT) is feasible. Existing CIT research supports the presence of main effect differences between persons concealing information and the control group. These behaviors may permit the detection of concealed information without the use of customized sets of stimuli. Eliminating the need to create customized sets of stimuli for each examinee would drastically increase the ease with which an automated system can be used to conduct a CIT. Finally, research is needed to illuminate various elements of the human-computer interaction that occurs during automated credibility assessments. This is a new domain of human-computer interaction as system users in this context are not instigating the interaction, and in many cases, they may be seeking to limit the effectiveness of the system. Before novel systems designed to conduct credibility assessments can be adopted, further research is needed to illuminate how users perceive, respond to, and strategically manage their behaviors when interacting with systems of this nature. This dissertation contains the results of a research program designed to address each of these areas. First, an experiment was designed to investigate the accuracy rates of two promising noncontact measures of concealed information (oculometrics and vocalics) relative to electrodermal activity (EDA). Second, an experiment was designed to evaluate the feasibility of using a targetless CIT to elicit main effect differences between concealers and the control group to identify concealed information. And third, a thorough analysis of examinees' general perceptions, self-reported stress and arousal, perceived effort and performance, and use of countermeasures within the context of an automated credibility assessment interview was conducted. This research effort has yielded the following findings. First, eye tracking and vocalics can be used to identify significant differences in the behaviors and physiology of examinees concealing information, however, the accuracy with which truth tellers and information concealers can be classified remains impractical for an applied setting. Second, there are main effect differences between persons concealing information and telling the truth, however, the use of countermeasures may limit the accuracy with which concealers can be identified. Finally, the presence of concealed information and the use of crime-relevant questions alter how examinees perceive and react to a system designed to identify concealed information. The limitations of this research, as well as directions for future research, are discussed.
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Swanström, Emma. "That's when we uncover : En studie om jämställdhetsdebatten kring artisten Zara Larsson." Thesis, Umeå universitet, Institutionen för kultur- och medievetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-119249.
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”That’s when we uncover” is an ethnolocical study of the discourse on gender equality surrounding commercial pop stars, based on the debate evolving the Swedish singer Zara Larsson. In the summer of 2015, the seventeen year old singer criticized a major festival in Sweden, Bråvalla, for their lack of women represented among their headlines. She also questioned why she was to perform at 1.15 pm, since she was the artist who was the most popular at Spotify of all playing at the festival. In addition to that, she criticized Bråvalla for not putting her name at their posters. Zara Larssons critique generated harsh words from another, male artist, wich lead to a debate in Swedish media all through the summer. Zara Larsson was defended by both other musicians, and by politicians, but she also got thousands of offensive comments at social medias, and received threats from men who claimed they wanted to see her raped, or dead. Zara Larsson has since then continued to provoke, through feminist statements, combined with exposing pictures of herself. The study is based on articles found in the media online, and on the debate in social medias. Three pictures posted by Zara Larsson at Instagram was chosen to represent what makes her so provocative, and the following comments was analyzed through a discoursive perspective. The study showed that the discourse can be divided in two: The discourse on gender equality in the statistics among artists at festivals, and the discourse on norms surrounding female artists. Those two are connected, and represents the two dimensions quantity and quality when it comes to gender equality. The study also showed that the strong reactions to Zara Larssons opinions was related to her subject position as a young, female singer within the commercial pop music business, and that there is a hegemony saying that male artist are the norm at festivals. The discourse also says that the over-representation of men performing at festivals are fair, and that young, female artists should have a limited space when it comes to actions and expressing opinions, compared to their male peers.
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Swanström, Emma. "That's when we uncover : En analys av jämställdhetsdebatten kring artisten Zara Larsson." Thesis, Umeå universitet, Institutionen för kultur- och medievetenskaper, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-116185.
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”That’s when we uncover” is an ethnolocical study of the discourse on gender equality surrounding commercial pop stars, based on the debate evolving the Swedish singer Zara Larsson. In the summer of 2015, the seventeen year old singer criticized a major festival in Sweden, Bråvalla, for their lack of women represented among their headlines. She also questioned why she was to perform at 1.15 pm, since she was the artist who was the most popular at Spotify of all playing at the festival. In addition to that, she criticized Bråvalla for not putting her name at their posters. Zara Larssons critique generated harsh words from another, male artist, wich lead to a debate in Swedish media all through the summer. Zara Larsson was defended by both other musicians, and by politicians, but she also got thousands of offensive comments at social medias, and received threats from men who claimed they wanted to see her raped, or dead. Zara Larsson has since then continued to provoke, through feminist statements, combined with exposing pictures of herself. The study is based on articles found in the media online, and on the debate in social medias. Three pictures posted by Zara Larsson at Instagram was chosen to represent what makes her so provocative, and the following comments was analyzed through a discoursive perspective. The study showed that the discourse can be divided in two: The discourse on gender equality in the statistics among artists at festivals, and the discourse on norms surrounding female artists. Those two are connected, and represents the two dimensions quantity and quality when it comes to gender equality. The study also showed that the strong reactions to Zara Larssons opinions was related to her subject position as a young, female singer within the commercial pop music business, and that there is a hegemony saying that male artist are the norm at festivals. The discourse also says that the over-representation of men performing at festivals are fair, and that young, female artists should have a limited space when it comes to actions and expressing opinions, compared to their male peers.
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Corsini, Julien. "Analysis and evaluation of network intrusion detection methods to uncover data theft." Thesis, Edinburgh Napier University, 2009. http://researchrepository.napier.ac.uk/output/4031/.
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Nowadays, the majority of corporations mainly use signature-based intrusion detection. This trend is partly due to the fact that signature detection is a well-known technology, as opposed to anomaly detection which is one of the hot topics in network security research. A second reason for this fact may be that anomaly detectors are known to generate many alerts, the majority of which being false alarms. Corporations need concrete comparisons between different tools in order to choose which is best suited for their needs. This thesis aims at comparing an anomaly detector with a signature detector in order to establish which is best suited to detect a data theft threat. The second aim of this thesis is to establish the influence of the training period length of an anomaly Intrusion Detection System (IDS) on its detection rate. This thesis presents a Network-based Intrusion Detection System (NIDS) evaluation testbed setup. It shows the setup of two IDSes, the signature detector Snort and the anomaly detector Statistical Packet Anomaly Detection Engine (SPADE). The evaluation testbed also includes the setup of a data theft scenario (reconnaissance, brute force attack on server and data theft). The results from the experiments carried out in this thesis proved inconclusive, mainly due to the fact that the anomaly detector SPADE requires a configuration adapted to the network monitored. Despite the fact that the experimental results proved inconclusive, this thesis could act as documentation for setting up a NIDS evaluation testbed. It could also be considered as documentation for the anomaly detector SPADE. This statement is made from the observation that there is no centralised documentation about SPADE, and not a single research paper documents the setup of an evaluation testbed.
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Santos, Raquel Alexandra Martinho dos. "Novel functions of the cohesin accessory factor dPDS5 uncover a new meiotic checkpoint." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2014. http://hdl.handle.net/10362/12072.
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Dissertation presented to obtain the Ph.D degree in Biology.Meiosis is a highly specialized type of cell division that is essential for sexual reproduction in all Eukaryotic species, where in two rounds of chromosome segregation take place without an intervening DNA replication phase (Petronczki et al., 2003). Genetic recombination during meiosis allows for the increase of genetic variability; furthermore, it is known that, at least in males, some level of chromatin reorganization occurs, such as histone displacement (White-Cooper and Davidson, 2011). Recombination requires the induction of endogenous Double Strand Breaks (DSBs), leading to the activation of a DNA Damage Response (DDR), that both recruits repair proteins and stalls the cell cycle until repair is completed (Harper and Elledge, 2007). Until now no surveillance pathway has been described that assures proper meiotic chromatin organization. In this work, we present evidence for the existence of such a surveying mechanism.(...)
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Walters, Ashley Daniell. "Using multiple lines of evidence to uncover hidden biodiversity in desert spring ecosystems." Miami University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1533045376808751.
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Mukherji, Proshanto. "Laws in logical worlds : using statistical inference to uncover the structure of logical domains /." Saarbrücken : VDM Verlag Dr. Müller, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?u20=9783836454377.
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Kling, Leslie A. "Using metaphorical techniques in focus groups to uncover feelings of mothers toward family meals." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 85 p, 2008. http://proquest.umi.com/pqdweb?did=1459903861&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Jaishankar, Gayatri, and Deborah Thibeault. "Screen, Uncover, Connect: A Hands-on Approach to Elucidating the Social Determinants of Health." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/8870.
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Jaishankar, Gayatri, Deborah Thibeault, and Angelica Johnson. "Screen, Uncover, Connect: A Hands-on Approach to Elucidating the Social Determinants of Health." Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/8871.
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Mukherji, Proshanto. "Laws in logical worlds using statistial inference to uncover the structure of logical domains." Saarbrücken VDM Verlag Dr. Müller, 2006. http://d-nb.info/989451313/04.
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Stokes, Mindy. "Women, Domestic Abuse, And Dreams: Analyzing Dreams To Uncover Hidden Traumas And Unacknowledged Strengths." [Tampa, Fla.] : University of South Florida, 2004. http://purl.fcla.edu/fcla/etd/SFE0000425.
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Bharathan, Navaneetha Krishnan. "USING THE FROG EPIDERMIS TO UNCOVER DESMOSOME FUNCTION AND REGULATION IN THE DEVELOPING EMBRYO." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5313.
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The desmosome is one of the major cell adhesion junctions found in the epithelia, heart, and hair follicle. Described as a “rivet” that hold cells together, it provides these tissues with the integrity to withstand the tremendous forces they face in everyday life. Defects in this junction can lead to devastating diseases where patients are susceptible to skin infections and cardiovascular defects. Limited treatments exist for diseases of the desmosome, and strategies do not target all symptoms. Therefore, delineating the function and regulation of desmosomes is of paramount importance for the development of prevention and treatment strategies. The Xenopus laevis has been utilized for the study of embryonic development and tissue movements. This study takes advantage of the frog model to study a key desmosomal protein, desmoplakin (Dsp), in the epidermal development of the embryo. First, Xenopus embryonic epidermis has junctional desmosomes as early as the blastula stages. Desmosomes numbers per junction increase as the embryo develops. Dsp is present in many epidermally-derived structures in the embryo at varying levels. Xenopus embryos deficient in desmoplakin have phenotypic defects in epidermal structures and the heart, mimicking mammalian models. Embryos with reduced Dsp exhibit an increased susceptibility to epidermal damage under applied mechanical forces. Assays also reveal a potential role for desmosomes in radial intercalation, a process through which cells move from the inner to the outer epidermal layers. Embryos with reduced Dsp exhibit a slight reduction in intercalation and defects in intercalating cell types, including multiciliated cells and small secretory cells. Finally, c-Jun N-terminal kinase (JNK) may have a potential role in the regulation of desmosome assembly and adhesion. Embryos with deficient Dsp display a partial recovery of mechanical integrity when treated with a JNK inhibitor.
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Freidhoff, Paul. "Using RNA Mimicry of Viroids to Uncover New Noncoding RNA Structural Motifs and Pathways." Thesis, University of the Sciences in Philadelphia, 2020. http://pqdtopen.proquest.com/#viewpdf?dispub=27665966.
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There is broad interest in ncRNAs within technology. The functions of ncRNAs are linked to RNA structural elements, but most of the structure-function relationships of ncRNAs are unknown, which limits the use RNA in technology. Viroids are the first ncRNAs observed. They are unique pathogens because they exclusively hijack ncRNA pathways by mimicking structures found in cellular RNAs. This makes viroids excellent models to study structural-functional relationships of cellular ncRNAs. In this research, we studied a structural element, the sarcin/ricin domain motif, found in PSTVd. This structural element is important in replication and processing, but the same structural element was not found in all viroids belonging in the Pospiviroidae family (a family of biochemically related viroids) using traditional methods including secondary structure prediction. Viroids in the Pospiviroidae utilize similar biochemical pathways including replication and RNA processing pathways. Furthermore, they utilize similar cellular factors in the processing and replication pathways so we have hypothesized that every Pospiviroidae forms a similar structural element like an SRD. We used computational methods including alignment, molecular dynamics, and RNA footprinting to show that every Pospiviroidae could form an SRD-like motif. The work also suggests that there could be undiscovered subsets of SRD mimics. The knowledge of conserved structural elements in RNA processing could be applied in RNA technology. In addition to structural analysis, our work resulted in the development of new analysis methods. These included an enrichment method to remove large RNAs from an RNA mixture without the removal of small to moderate sized RNAs. We have also progressed in developing a new cell-based RNA assay which will analyze the effects of cellular biochemical factors on viroid processing.
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Yang, Qi. "A system biology approach to uncover the regulatory and effector hubs of Rac-family GTPases." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121446.
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Rho-family proteins are a major branch of the Ras superfamily of small GTPases. These proteins can be further subdivided into six subfamilies according to primary amino acid sequence identity, structural motifs and biological function: Rho, Cdc42, Rac, RhoBTB, RhoT and Rnd subfamily. Rho-family proteins are "molecular switches" and cycle between GDP-bound "inactive" state and GTP-bound "active" state by regulation of guanine nucleotide exchange factors (GEFs) and GTPases-activating proteins (GAPs). Rho GTPases have a large collection of effectors and are involved in numerous cellular and physiological processes, such as cytoskeletal reorganization, microtubule dynamics, cell polarity, gene expression and cell cycle progression. However, it is poorly understood how Rho GTPases select specific effectors for diverse physiologic functions. We hypothesize that the specificity of effector choice is dictated by the individual GEF or by scaffold proteins binding either the GEF or the Rho proteins. To test this hypothesis, I used a system biology approach which will determine the complete interactome of the Rac GTPases (Rac1, Rac2, Rac3, and RhoG) in their active and inactive conformation. Through this method, we tried to discover new Rac effectors, possible molecular scaffolds and the Rac:GEF and Rac:GAP specificity.Les protéines de la famille Rho forment une branche majeure de la superfamille des petites GTPases Ras. Ces protéines peuvent être subdivisées en six sous-familles selon leur identité de séquence d'acides aminés primaires, leur motifs structuraux et leur fonction biologique, soient les sous-familles: Rho, Cdc42, Rac, RhoBTB, RhoT et Rnd. Les petites GTPases agissent comme des "interrupteurs moléculaires" soit qu'elles vont osciller entre un état "inactif" (GTPase-GDP) et un état "actif" (GTPase-GTP), et ce cycle est régulé par des facteurs d'échange de nucléotides guanine (GEFs) et des protéines activatrices de GTPases (GAPs). Les GTPases Rho ont une multitude d'effecteurs et elles sont impliquées dans de nombreux processus cellulaires et physiologiques, tels que la réorganisation du cytosquelette, la dynamique des microtubules, la polarité cellulaire, l'expression génique et la progression du cycle cellulaire. Cependant, il est encore mal compris comment les GTPases Rho sélectionnent des effecteurs spécifiques pour les différentes fonctions physiologiques. Nous émettons l'hypothèse que le choix de l'effecteur est dictée par la GEF impliquée ou par une protéine d'échafaudage qui est soit liée à la GEF ou à la GTPase. Pour tester cette hypothèse, j'ai utilisé une approche de la biologie des systèmes qui déterminera l'interactome complet des GTPases Rac (Rac1, Rac2, RAC3 et RhoG) dans leur conformation active et inactive. Grâce à cette méthode, nous avons essayé de découvrir des nouveaux effecteurs de Rac, des protéines d'échafaudage, ainsi que des GEFs et des GAPs spécifiques pour Rac.
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Oakgrove, Francis. "Intellectual and Experiential Knowing: An Exploratory Factor Analysis to Uncover the Underlying Structure of Knowing." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29886.
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Knowledge and the acquisition thereof have long been debated throughout human history. Several authors have suggested that knowing and knowledge differ among people. However, there is consistency among these studies that suggests a dualism within Western philosophy where a person exists of a mind and a body?two distinct and separate entities?with the mind as the central point of knowing. The theoretical framework for this study suggests that the dualism representation is limiting. Further, it posits that the body is also a central point for knowing. Hence, the Ways of Knowing Scale (WoKS) was developed in an attempt to measure the two separate ways of knowing through two subscales: experiential knowing (EK) and intellectual knowing (IK). This study serves as a presentation of the theoretical and philosophical framework for the WoKS as well as a pilot study and psychometric analysis. Exploratory factor analysis (EFA) was implemented using data collected from a sample of n = 686 respondents on an initial pool of 22 items. Each of these items was constructed to reflect one of the two proposed constructs, hence two subscales (11 items per subscale). Although two constructs were originally hypothesized, a three-factor solution exhibited the closest approximation to simple structure; further, the three factors provided the most interpretable and meaningful solution. Two of the factors appear to correspond to the two original constructs suggested by theory. The various potential explanations for this third factor are considered. Future research is needed to further explore the nature of this emergent factor and subsequently refine the WoKS.
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Ahmad, Fahmida. "Modelling heterogeneity of triple-negative breast cancer in mice to uncover and target signaling essentiality." Thesis, Aix-Marseille, 2020. http://www.theses.fr/2020AIXM0225.
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Le cancer du sein triple négatif (TNBC) est un sous-type de cancer du sein très agressif et hétérogénène qui ne bénéficie actuellement d'aucun traitement efficace. Le but de mon projet de Thèse était d'explorer les mécanismes qui conduisent au TNBC pour concevoir de nouvelles approches thérapeutiques.Dans notre équipe, nous avons généré un modèle de souris unique (souris MMTV-R26Met) dans lesquelles le récepteur tyrosine kinase MET est faiblement augmenté. Elles développent spontanément et exclusivement des TNBC. Ce modèle récapitule la formation de métastases pulmonaires, la résistance aux agents chimiothérapeutiques classiques et à un ensemble de thérapies moléculaires ciblées combinées.Une analyse protéomique des tumeurs MMTV-R26Met combinée à une approche de type "machine learning" ont montré que le modèle MMTV-R26Met récapitule largement l'hétérogénéité du TNBC observée chez les patients TNBC.Nous avons identifié deux nouvelles combinaisons d'agents très délétères pour les lignées cellulaires dérivées de tumeurs MMTV-R26Met et un panel de cellules TNBC humaines. La première cible le facteur anti-apoptotique BCL-XL et CDK1/2 (régulateurs du cycle cellulaire). La deuxième, validée in vivo, agit sur BCL-XL et WEE1 (régulateur du cycle cellulaire et épigénétique). Mécanistiquement, nous montrons que le ciblage combiné de WEE1 et de BCL-XL induit des dommages à l'ADN, une entrée prématurée en mitose, une catastrophe mitotique et l'apoptose.Nos travaux peuvent être très pertinents pour leur transposition potentielle à la clinique, compte tenu également des études prometteuses de monothérapie avec les inhibiteurs de BCL-XL et WEE1 dans les essais cliniques de phase IITriple-negative breast cancer (TNBC) is a highly aggressive, heterogeneous breast cancer subtype, and has currently no effective treatment. The aim of my PhD project was to understand the mechanisms triggering TNBC and to develop new therapeutic approaches.In our lab, we have generated a unique mouse model (MMTV-R26Met mice) in which a subtle increase in the expression levels of the wild-type MET receptor tyrosine kinase leads to spontaneous, exclusive TNBC formation. This model recapitulates formation of lung metastasis, resistance to conventional chemotherapeutic agents and to a set of combined targeted molecular therapies.Proteomic profiling of MMTV-R26Met tumors and machine learning approach showed that the MMTV-R26Met model largely recapitulates TNBC heterogeneity observed in TNBC patients. We identified two new drug combinations highly deleterious for the MMTV-R26Met tumor-derived cell lines, and a panel of human TNBC cells. The first drug combination targets the anti-apoptotic factor BCL-XL and CDK1/2 (cell cycle regulators). The second drug combination, validated by in vivo studies, is based on a combinatorial targeting of BCL-XL and of WEE1 (cell cycle and epigenetic regulator). Mechanistically, we show that combined inhibition of WEE1 and BCL-XL leads to DNA damage, premature entry into mitosis, resulting in mitotic catastrophe and apoptosis.Our findings may be highly relevant for their potential translation to the clinic, also in view of promising studies of monotherapy with BCL-XL and WEE1 inhibitors in phase II clinical trials
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Baranowski, B. "Chemical screening to uncover small molecules that modulate neural stem cell self-renewal and differentiation." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1468463/.
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In vitro expanded neural stem cells provide an important cellular model to explore mechanisms of neural development, for modelling of disease, and in the longer term may have applications in new types of stem cell-based therapies. However, our ability to steer neural stem (NS) cell lines into specific desired lineages in vitro remains limited. PDGFRα is one of the earliest markers of the transition of neural stem cells to oligodendrocyte progenitors. I established and characterised a novel set of mouse NS cell lines that report the activation of PDGFRα via expression of an H2B:GFP ‘knock-in’. Three clonal ‘PG1’ cell lines were fully characterised. Under self-renewing conditions I found <1% of NS cell express the H2B:GFP reporter but this increases to ~15-20% following induction of differentiation. Using this cellular model system I carried out a high-content chemical screen of a diverse collection of 463 pharmacologically active small molecule modulators of ‘stem cell pathways’ and kinase inhibitors, to identify those capable of modulating NS cell self-renewal and differentiation. I did not uncover any small molecules capable of promoting OPC lineage specification. However, I found multiple HDAC inhibitors that were highly effective in blocking the activation of PDGFRα, a finding that mirrors published studies implicating HDAC inhibition in the later differentiation of OPCs to oligodendrocytes. Three further compounds, Nigericin (an ionophore), Withaferin (a steroidal lactone) and NFkB inhibitor also completely blocked OPC commitment. I focused on the specific cellular responses and downstream molecular events triggered by these molecules and tested their differentiation potential on human NS cells and malignant glioblastoma-derived NS cells.
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Sánchez, Arroyo Alicia 1989. "Metabarcoding of the 18S rRNA gene to uncover new molecular biodiversity in Metazoa and unicellular Opisthokonta." Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/667270.
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One of the main evolutionary transitions is the origin of animal and fungal multicellularity from single-cell ancestors. To address this change, it is necessary to study the extant unicellular relatives of animals (Metazoa) and fungi, all of them forming the Opisthokonta clade. Recent data have shown that adding more taxa to the Opisthokonta tree can dramatically change our view on this transition. However, the real diversity of these organisms is mostly unknown. Therefore, the main goal of this Ph.D. was to analyse the molecular diversity of both microbial opisthokonts as well as animals, searching for genetic novelty in the form of potential novel clades, as well as trying to better understand their ecology. Using Next-Generation Sequencing data, mainly metabarcoding based on the universal marker 18S rRNA gene, I have performed phylogenetic and ecological inferences, together with graph analysis, to unravel new undescribed diversity of Opisthokonta organisms.Una de las principales transiciones evolutivas es el origen de la multicelularidad en animales y hongos a partir de sus ancestros unicelulares. Para entender este cambio es necesario estudiar a los organismos unicelulares más próximos evolutivamente a los animales (Metazoa) y hongos, formando todos ellos el clado Opisthokonta. Se ha comprobado que añadir información genética de más especies al árbol de los opistocontos puede cambiar drásticamente nuestra visión de dicha transición. Sin embargo, la diversidad real de estos linajes es prácticamente desconocida. Por tanto, el principal objetivo de este doctorado ha sido analizar la diversidad molecular de los opistocontos unicelulares y de animales para buscar novedad genética en forma de nuevos clados y, a la vez, entender su ecología. Usando datos de Secuenciación de Nueva Generación, principalmente metabarcoding del gen universal 18S rRNA, he realizado inferencias filogenéticas y ecológicas, junto con análisis de redes para descubrir nueva diversidad de organismos opistocontos desconocidos.
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Paulson, Courtney L. "Using the Haar-Fisz wavelet transform to uncover regions of constant light intensity in Saturn's rings." Honors in the Major Thesis, University of Central Florida, 2010. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1473.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Sciences
Statistics
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Tafreshian, Kimia [Verfasser]. "A screen to uncover mediators of resistance to liver X receptor agonistic cancer therapy / Kimia Tafreshian." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1228859833/34.
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Francisco, Rita. "Biochemistry of grape berries: post-genomics approaches to uncover the effects of water deficits on ripening." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2011. http://hdl.handle.net/10362/6185.
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Dissertation presented to obtain the Ph.D degree in Biochemistry,
Plant PhysiologyGrapevine (Vitis vinifera L.) is one of the most important fruit crops worldwide. In Europe, high-quality wine producing areas are traditionally non-irrigated. However, irrigation has become a wide-spread agronomical practice to overcome the deleterious effects of drought, high temperature and high evaporative demand that vines can be exposed to during the growing season. This is particularly true in the Mediterranean area, where the foreseen scenario predicts that water deficit may become a limiting factor in wine production and quality. Paradoxically, the imposition of mild to moderate water deficit (WD) via e.g. water deficit irrigation has been regarded as an agronomical tool that manipulates berry sensory characteristics, while maintaining yield. Grape berries, which are described as non-climacteric fruits, undergo a complex biochemical suite of alterations during development and ripening that remain poorly understood, including the molecular events that control the onset of ripening. At harvest, grape berry quality is largely dependent on the sugar/acids balance within the berry flesh, and on phenolic compounds (e.g. flavonoids) in the grape skin, which contribute to wine colour, aroma and flavour.(...)
PhD Fellowship SFRH/BD/30344/2006 from ‘Fundação para a Ciência e a Tecnologia’ (FCT) and ‘Fundo Social Europeu’ in the scope of ‘Quadro Comunitário de Apoio’.
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Kent, Robyn. "Experimentally inducible gametocytogenesis : a new tool to uncover the early stages of commitment in P. berghei." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/8135/.
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Plasmodium, the causative agent of malaria, has a complex life cycle requiring a mammalian host and a mosquito vector. Its cyclic infection of red blood cells gives rise to the characteristic fevers and resulting anaemia associated with the disease. Many drug intervention strategies target this, the asexual blood cycle. Little is known about the underlying processes governing the differentiation from this cycle to the sexual stage, the gametocyte, which is uniquely able to transmit through the mosquito to new hosts. In this work we have developed a novel conditional system to build on existing knowledge about the trigger for sexual commitment (ap2-g) to control and expand commitment to gametocytogenesis in the rodent malaria model, Plasmodium berghei. We have characterised the effect of controlling and increasing expression of this initiating transcription factor on asexual and gametocyte development in an effort to obtain an over representation of biologically relevant gametocytes. Using this novel system we initiated an untargeted transcriptomics study to uncover novel factors involved in the process of commitment and other gametocyte specific roles such as gender assignation, sex specific components and overall gametocyte development. From the pilot data obtained from this transcriptomics we identified and screened 40 candidates potentially specifically involved in gametocyte biology. Five of these candidates have been investigated further to uncover novel roles in the early stages of commitment or development (2 gametocyte non-producers), male specific development (1 male non-producer and 1 which seems to effect development) and potentially female specific development (1 in vivo female non-producer). Using the data generated in this study we hope further work can be completed to characterise many aspects of commitment to gametocytogenesis and the processes involved in downstream events required for successful transmission.
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Karlsson, Karin, and Lamei Tang. "Consistency in Constant Change : A Sensemaking Perspective to Uncover How Marketers Justify Budget for Branding Activities." Thesis, Linköpings universitet, Företagsekonomi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-177730.
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Title: Consistency in Constant Change: A Sensemaking Perspective to Uncover How Marketers Justify Budget for Branding Activities. Background: Branding activities are part of marketers’ everyday work life and have increased in organisational importance of how marketing is conducted. However, due to the lack of a direct linkage to conversion, branding activities are challenging to know the output of. Despite this, marketers continue to spend part of the marketing budget on branding activities. To understand how marketers justify decisions for branding activities, this Thesis views justifying branding activities as a wicked problem. It uses decision-making theory with a sensemaking lens to uncover patterns of decision input and output. Purpose: Taking the organisational perspective, this study seeks to clarify and bring insights into how branding decisions are justified by surfacing underlying patterns when marketers justify decisions for branding activities. Methodology: This Thesis uses an abductive qualitative study approach. To uncover the problem and guide the study direction, 12 pre-interviews were conducted. Then, a literature review and 12 in-depth, exploratory and semi-structured interviews with marketing professionals were conducted to understand directly from the budget owners regarding how budget is justified for branding activities. Findings: The introduced conceptual framework shows that justifying branding activities is an ongoing process that faces constant change. Three main patterns are found for how marketers justify budget for branding decisions. First, marketers clarify what identity and preference to use by identifying ‘what matters’ during the decision-making process and they either claim or share the right of deciding. Second, a general understanding is that branding activities are immeasurable in nature and marketers tell a plausible story of their effectiveness by measuring what can be measured, measure changes, or use financial results as a final judge. Third, internal and external constraints exist throughout the process of justifying branding activities, including technology limitations, loss of other’s branding sense, and limited budget and resources.
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Çergani, Ervina [Verfasser], Mira Akademischer Betreuer] Mezini, and Christoph-Matthias [Akademischer Betreuer] [Bockisch. "Machine Learning as a Mean to Uncover Latent Knowledge from Source Code / Ervina Cergani ; Mira Mezini, Christoph Bockisch." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://nbn-resolving.de/urn:nbn:de:tuda-tuprints-116586.
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Çergani, Ervina [Verfasser], Mira [Akademischer Betreuer] Mezini, and Christoph [Akademischer Betreuer] Bockisch. "Machine Learning as a Mean to Uncover Latent Knowledge from Source Code / Ervina Cergani ; Mira Mezini, Christoph Bockisch." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1211088456/34.
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Cergani, Ervina [Verfasser], Mira [Akademischer Betreuer] Mezini, and Christoph [Akademischer Betreuer] Bockisch. "Machine Learning as a Mean to Uncover Latent Knowledge from Source Code / Ervina Cergani ; Mira Mezini, Christoph Bockisch." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2020. http://d-nb.info/1211088456/34.
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Plack, Leah. "Using the Task Analysis Process with Teachers to Uncover Language Demands within an Eight-Week NGSS Summer Course." PDXScholar, 2017. https://pdxscholar.library.pdx.edu/open_access_etds/4014.
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The state of Oregon has adopted the Next Generation Science Standards as well as the English Language Proficiency standards, both of which affect elementary school teachers. These standards adoptions challenge teachers and professional developers to rethink how they approach science conceptual understanding and language acquisition. The Math Science Partnership K-6 Instructional Specialist Grant made the decision to incorporate a Task Analysis process, which asks the participant to analyze the demands of a content-based task in the domains of content knowledge, analytical skills and language, into six eight-week summer courses focused on the Next Generation Science Standards. A pre and post-assessment was created to determine if any growth in teacher understanding of the demands of a science task could be observed as a result of engaging in the Task Analysis process. A four point rubric was created to score participant responses. Two research questions were developed: 1. How well does the ELPA21 Task Analysis tool help participants understand the language demands of a science task when used as part of an NGSS summer professional development course? 2. How effective is a work sample and scoring rubric protocol for measuring the impact of the Task Analysis process? Participants showed statistically significant growth in their analysis of a science task from pre to post-assessment responses, with particularly strong growth demonstrated in the domains of content and language. Further coding of responses revealed that participants frequently discussed vocabulary as both a language and content knowledge demand of a science task.
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Soboleski, Penny K. "THE HIDDEN CHILDREN OF THE CLASSROOM: A VALIDATION STUDY USING ALTERNATIVE ASSESSMENTS TO UNCOVER THIRD-GRADE READERS WITH DYSLEXIA." Connect to this title online, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=bgsu1143482871.
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Suryavanshi, Gajendra [Verfasser], and Roland [Akademischer Betreuer] Eils. "Mathematical model to uncover the role of receptor ubiquitination in dose dependent EGFR trafficking / Gajendra Suryavanshi ; Betreuer: Roland Eils." Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://d-nb.info/1179783727/34.
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Watts, Sarah. "Investigation to uncover the electrophysiological correlates of the mediating cognitive factors, responsible for the immediate emotional enhancement of memory." Thesis, Durham University, 2015. http://etheses.dur.ac.uk/11069/.
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Emotional memories are powerful memories that have markedly different phenomenological characteristics, compared to neutral memories. Emotional memories are adaptive and serve to aid survival of organisms. Evidence suggests that emotional events tend to be remembered with a greater depth of sensory and perceptual detail. The phenomenon around such memories has therefore been coined, emotion-enhanced memory (EEM). Much of the research into EEM has focused on the long-term consolidating affects that emotions can have upon memory; with the modulation hypothesis being the predominant theory in the literature. However, it has been noted in the literature that emotional stimuli can also enhance short-term memories, immediately after test. It is suggested that the immediate EEM is driven by changes in the cognitive attributes of emotional stimuli, which facilitates encoding processes; this is known as the cognitive-mediating account of immediate EEM. This research aims to investigate three of the key cognitive mediating factors, implicated in the behavioural literature; distinctiveness, relatedness and attention. Using electrophysiological recordings and event-related potentials, this work aims to further the behavioural research and develop functional accounts of how these cognitive factors can influence the immediate EEM. The results suggest that distinctiveness plays a significant role in the immediate EEM and a functional two-step model is proposed to outline the mechanisms through which it exerts it influence. This works also suggests overt attentional resources play a key role, as part of distinctiveness processing. The results did however find, contrary to the behavioural literature, relatedness is unable to fully account for the immediate EEM. These results are interpreted as supporting a complimentary model of EEM, which involves both the cognitive-mediating account for the immediate EEM and the modulation hypothesis for long-term EEM. These findings are discussed in terms of the real-world implications that emotional memory research can have.
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Suryavanshi, Gajendra Wamanrao [Verfasser], and Roland [Akademischer Betreuer] Eils. "Mathematical model to uncover the role of receptor ubiquitination in dose dependent EGFR trafficking / Gajendra Suryavanshi ; Betreuer: Roland Eils." Heidelberg : Universitätsbibliothek Heidelberg, 2012. http://nbn-resolving.de/urn:nbn:de:bsz:16-opus-131084.
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Ramos, Vicente David. "Phylogenetic Studies of Glutamate Receptors and their Auxiliary Subunits Update their Classifications and Uncover their Diverse Metazoan Evolutionary Histories." Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/673959.
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El glutamat és el principal neurotransmissor excitatori en el sistema nerviós dels vertebrats i invertebrats. Les proteïnes involucrades en la neurotransmissió glutamatèrgica, i especialment els receptors de glutamat i les seves subunitats auxiliars, juguen un paper clau en el funcionament del sistema nerviós. Així, entendre la seva evolució i revelar la seva diversitat és essencial per comprendre com ha evolucionat el sistema nerviós, donant forma a la funció cognitiva. L'anàlisi integral de la filogènia d'aquestes proteïnes en els metazous ha revelat que la seva evolució és molt més complexa del que es podia anticipar en base al genoma dels vertebrats. Això és particularment cert per als receptors ionotròpics de glutamat, doncs la seva classificació actual en sis classes (AMPA, Kainat, Delta, NMDA1, NMDA2 and NMDA3) seria altament incompleta. El treball presentat aquí proposa una classificació en 4 subfamílies que engloben 10 classes. Els receptors AMPA, Kainat i Delta de vertebrats pertanyerien a una d'aquestes subfamílies, anomenada AKDF, i les subunitats NMDA constituirien una altra subfamília. A més, també podrien existir dues subfamílies no descrites previament, que són referides com a Epsilon i Lambda. D'una altra banda, les famílies de proteïnes que contenen subunitats auxiliars de receptors AMPA (ARAS) han experimentat històries evolutives menys complexes. No obstant, els vertebrats haurien reclutat per actuar com ARAS a la sinapsi proteïnes d'aquestes famílies per processos de neo i/o subfuncionalització donats després d'events de duplicació gènica ocorreguda en aquest llinatge. Així aquest treball afavoreix la hipòtesi que la complexitat del sistema nerviós podria haver evolucionat no pas incrementant el conjunt de receptors de neurotransmissors en el genoma, sinó augmentant la regulació d'aquests receptors a la sinapsi.El glutamato es el principal neurotransmisor excitatorio del sistema nervioso de los vertebrados e invertebrados. Las proteínas involucradas en la neurotransmisión glutamatérgica, y especialmente los receptores de glutamato y sus subunitades auxiliares, juegan un papel clave en el funcionamiento del sistema nervioso. Así, entender su evolución y revelar su diversidad es esencial para comprender como ha evolucionado el sistema nervioso, dando forma a la función cognitiva. El análisis integral de la filogenia de estas proteínas en los metazoos ha revelado que su evolución es mucho más compleja de lo que se podia anticipar en base al genoma de los vertebrados. Esto es particularmente cierto para los receptores ionotrópicos de glutamato, pues su clasificación actual en seis clases (AMPA, Kainato, Delta, NMDA1, NMDA2 and NMDA3) estaría altamente incompleta. El trabajo aquí presentado propone una clasificación en 4 subfamilias que engloban 10 clases. Los receptores AMPA, Kainato y Delta de vertebrados pertenecerían a una de estas subfamilias, llamada AKDF, y las subunidades NMDA constituirían otra subfamilia. Además, también podrían existir dos subfamilias no descritas previamente, que son referidas como Epsilon y Lambda. Por otro lado, las familias de proteínas que contienen subunidades auxiliares de receptores AMPA (ARAS) han experimentado historias evolutivas menos complejas. No obstante, los vertebrados habrían reclutado para actuar como ARAS a la sinapsis proteínas de estas familias mediante procesos de neo y/o subfuncionalización que se dieron después de eventos de duplicación génica ocurridos en este linaje. Así este trabajo favorece la hipótesis de que la complejidad del sistema nervioso podría no haber evolucionado incrementando el conjunto de receptores de neurotransmisores en el genoma, sino augmentando la regulación de estos receptores en la sinapsis.
Glutamate is the major excitatory neurotransmitter in vertebrate and invertebrate nervous systems. Proteins involved in glutamatergic neurotransmission, and chiefly glutamate receptors and their auxiliary subunits, play key roles in nervous system function. Thus, understanding their evolution and uncovering their diversity is essential to comprehend how nervous systems evolved, shaping cognitive function. Comprehensive phylogenetic analysis of these proteins across metazoans have revealed that their evolution is much more complex than what can be anticipated from vertebrate genomes. This is particularly true for ionotropic glutamate receptors, as their current classification in six classes (AMPA, Kainate, Delta, NMDA1, NMDA2 and NMDA3) would be largely incomplete. New work proposes a classification into 4 subfamilies that encompass 10 classes. Vertebrate AMPA, Kainate and Delta receptors would belong to one of these subfamilies, named AKDF, and the NMDA subunits would constitute another subfamily. Furthermore, two previously unreported subfamilies would also exist, these are referred to as Epsilon and Lambda. On the other hand, protein families containing AMPA receptor auxiliary subunits (ARAS) have experienced less complex evolutionary histories. Nevertheless, vertebrates would have recruited to function as ARAS in the synapse proteins from these families by neo and/or subfunctionalization after gene duplication events occurred in this lineage. Thus, this work favours the hypothesis that nervous system complexity could have evolved not by increasing the set of neurotransmitter receptors in the genome, but by increasing the regulation of such receptors in the synapse.
Universitat Autònoma de Barcelona. Programa de Doctorat en Neurociències
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Camprubí, Font Carla. "Genetics and transcriptomics of adherent-invasive Escherichia coli (AIEC): new approaches to uncover molecular markers for its rapid identification." Doctoral thesis, Universitat de Girona, 2019. http://hdl.handle.net/10803/672302.
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The adherent-invasive Escherichia coli (AIEC) pathotype could play a role in the course of Crohn’s disease. This is characterized by its capacity to adhere to and to invade intestinal epithelial cells as well as to replicate and survive within macrophages. At present, identification of the AIEC pathotype relies on time-consuming techniques based on the phenotypic screening of cultured bacteria, which are not standardized. In this thesis, we focused on the study of AIEC genetics in order to look for key characteristics that could assist the development of a molecular tool for the identification of the pathotype.
To sum up, the results of this work provide meaningful information that contributes to our understanding of AIEC genomics. In this case, two putative molecular markers resulting from a combination of genetic and/or phenotypic features have been presented and these could assist in AIEC screening. Finally, gene expression results provide new insights to better describe genes putatively involved in AIEC virulenceEl patotip adherent-invasiu d’Escherichia coli (AIEC) podria jugar un paper en el transcurs de la malaltia de Crohn. Aquest es caracteritza per tenir capacitat d’adhesió i invasió a cèl·lules de l’epiteli intestinal a més de replicar-se i sobreviure en macròfags. Actualment la única manera d’identificar aquests bacteris és analitzant aquestes característiques fenotípiques, un mètode poc estandarditzat i que requereix molt temps i dedicació. En la present tesi ens hem centrat en estudiar genèticament el patotip AIEC per tal de buscar característiques clau que puguin ajudar en el desenvolupament d’una eina molecular per a la seva identificació. En resum, els resultats d'aquest treball proporcionen informació significativa que contribueix a la comprensió de la genètica del patotip AIEC. En aquest cas, s'han presentat dos possibles marcadors moleculars resultants d'una combinació de característiques genètiques i/o fenotípiques que podrien ajudar en la detecció d’AIEC. Finalment, els resultats d'expressió gènica proporcionen noves idees per descriure millor els gens implicats en la virulència del patotip AIEC
Programa de Doctorat en Biologia Molecular, Biomedicina i Salut
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Luippold, Benjamin Labrie. "Managing audits to manage earnings the impact of baiting tactics on an auditor's ability to uncover earnings management errors /." Amherst, Mass. : University of Massachusetts Amherst, 2009. http://scholarworks.umass.edu/open_access_dissertations/106/.
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Van, de Velde Caroline. "Monitoring eye movements to uncover the role of visual context in the access to verb-complement information during sentence comprehension." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ64022.pdf.
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Merz, Dale R. Jr. "Molecular simulations uncover the nanomechanics of heat shock protein (70 kDa) & Indentation simulations of microtubules reveal katanin severing insights." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583154342504106.
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Stewart, Michelle Elizabeth. "Development of high-throughput, non-invasive behavioural and cognitive tests in mice to uncover new mechanisms of abnormal cognition and behaviour." Thesis, Open University, 2018. http://oro.open.ac.uk/58323/.
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Cognition is a complex process encompassing a variety of traits, including the ability learn, remember, evaluate situations, make decisions and solve problems. Research over recent decades has begun to elucidate some of the mechanisms through which organisms carry out these complex behaviours, however there is a great deal that is not understood about the basic biology of cognition. Importantly, there is a deficit in our knowledge not only of the underlying biology but also the pathological mechanisms which lead to cognitive disease. Genetically altered mice have been developed that model some aspects of cognitive disease. However at present these models have helped to elucidate only certain elements of cognitive processes and many have had limited use in drug development. To further understand cognition and cognitive disease, as well as develop effective treatments, it is critical to have more genetically altered mouse lines that better model the human condition. To find such models we have employed a high-throughput screening approach. Firstly we assessed existing behavioural and cognitive tests for their suitability to high-throughput testing, we then incorporated the selected test, fear conditioning, into a high-throughput pipeline. 289 different genetically altered (GA) lines were screened using the fear conditioning protocol and GA lines with potentially interesting phenotypes selected for further analysis. Using this screening process Ferric chelate reductase 1-like (Frrs1l) was selected for more in-depth testing. On further investigation we found deletion of Frrs1l to cause increased neonatal mortality and abnormalities in activity, co-ordination, muscle strength, cognition and body weight, as well as seizures. These phenotypes appear to be caused by a dramatic reduction in AMPA receptor levels at the synapse, as well as mislocalisation of AMPA receptors and alterations in processing. In collaboration with clinicians we corroborated these findings with some newly identified patients with homozygous mutations in FRRS1L.
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Price, David Andrew. "Using Infrared Spectroscopy to Uncover Structure in Biomolecular Assemblies Related to Disease: Applications to Nucleic Acid and Peptide Oligomers and Aggregates." OpenSIUC, 2020. https://opensiuc.lib.siu.edu/dissertations/1845.
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The functional and pathogenic roles of biomolecules are often coupled to the self-association of their basic units into oligomers and aggregates whose structural details are difficult to distinguish because of their insoluble and heterogenous nature. This work focuses on DNA G-quadruplex motifs and amyloid peptides whose oligomers and aggregates are associated with numerous biological roles and human diseases. Infrared (IR) spectroscopy is a powerful tool which probes vibrational transitions whose signatures report on their arrangement within molecules. Advances in two-dimensional infrared (2D IR) spectroscopy have allowed structural characterization in increasingly complex biomolecules that are not amenable to traditional high-resolution techniques. However, careful consideration of the physical phenomena that lead to IR spectra are necessary to make accurate assignments. In the first portion of this work, using FTIR and 2D IR, we determine spectral markers that can differentiate size, metal ion coordination, and topology in DNA G-quadruplex motifs. IR studies aided by isotope labeling define the physical origin of these markers and allow for the construction of a structural landscape in parallel DNA G-quadruplex motifs. It is also shown that 2D IR and isotope editing probes site-specific structural changes in G-quadruplex motifs that can differentiate ion identity and location based on spectral shifts. In the latter portion of this work, we use a combination of spectroscopy and imaging techniques to show that a peptide derived from the human pro-apoptotic protein BAX forms amyloid aggregates whose structure is dependent on the presence of model membranes. Combined, the work in this thesis allows for the formulation of multiple hypotheses based on IR structural assignments regarding disease states and functional mechanisms of these systems.
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Brown, Donna Noelle. "Facilitating changes in the practice context: using action research to uncover the significance of psychological safety - an example from pain management with older people." Thesis, Ulster University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.490391.
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Background: The National Confidential Enquiry into perioperative deaths (NCEPOD, 1999) reported that the majority of older patients (65 years or over), notified to them, underwent surgery in hospitals with established Acute Pain Services (APS). Nevertheless, only a minority had basic pain assessment charts recorded. The Report subsequently recommended that pain teams must work towards addressing pain management issues that are particular to older people. However, research evidence in this field suggests that healthcare professionals experience difficulties in meeting the needs of older people and integrating evidence into daily practice. With the number of older people requiring surgery increasing, it is important to identify and address factors in the practice context that enhance or inhibit effective pain management. Aims: Working as a researcher/facilitator with healthcare staff in two acute surgical wards this project aimed to; (i) implement and evaluate a programme of development that enabled the team to critically analyse practice and put existing research into practice; (ii) develop an understanding of factors in the practice context that enhance or inhibit effective pain management; (iii) and develop effective team working to enhance pain management practices with older people. Methodology: Drawing upon an Emancipatory Action Research approach and utilising the Promoting Action on Research Implementation in Health Services (PARIHS) framework (Kitson et al 1998) to guide the study, nursing staff identified three overarching action cycles that appeared to impact upon pain management practices with older people (communication, interruptions, and pain assessment practices). Working with nursing staff, five focus groups, three workshops, eighteen reflective sessions, twenty-seven critical companionship meetings and twenty-six ad hoc meetings, were completed. To consolidate and affirm the data, nonparticipant observation of nursing practice was completed (46 hours), older patients were invited to participate in semi-structured interviews (n=6) and thirty (83%) registered nurses completed the Nursing Work Index-Revised questionnaire (NWI-R, Aiken and Patrician 2000). Results: Data analysis revealed the complexity of context. Clarification and refinement of the emerging themes resulted in the development of a conceptual framework. Three key themes (psychological safety, leadership, oppression) and four sub-themes (power, horizontal violence, distorted perceptions, autonomy) emerged as significant to nursing practice and context. Conclusion: It is argued that context, effective leadership and the creation of a psychologically safe environment have a significant impact upon all aspects of nursing practice (including pain management practices with older people) in the acute surgical setting. Facilitated reflective sessions and critical companionship created 'spaces' and supported individuals and groups to learn. This resulted in a culture that was more open and willing to work towards a shared vision for effective person-centred nursing practices.
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Dupont, Marie. "Étude fonctionnelle de gènes candidats impliqués dans les ciliopathies Human IFT52 mutations uncover a novel role for the protein in microtubule dynamics and centrosome cohesion." Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB006.
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Les ciliopathies sont des maladies multisystémiques dues à des mutations dans des gènes codant des protéines localisées au cil. Les cils sont des organites constitués de microtubules présents à la surface de quasi toutes les cellules de vertébrés. IFT52 est un composant majeur du complexe du transport intraflagellaire IFT-B, indispensable à la formation et fonction du cil primaire. Des mutations faux-sens, non-sens ou de délétion en phase ont été identifiées dans IFT52 chez des individus présentant des phénotypes distincts de ciliopathies : une dysplasie rénale multikystique (DRK) ou des dysplasies squelettiques de type côtes courtes-polydactylie (CCP) ou Sensenbrenner (SB). Afin de mieux comprendre la variabilité phénotypique, nous avons étudié la pathogénicité de chacune des mutations grâce à des modèles cellulaires et animaux. D'abord, j'ai montré que les mutations de délétion en phase (CCP) et non-sens (SB), mènent en fait respectivement à un décalage de phase de lecture et un saut d'exon en phase, ce qui permettait d'expliquer en partie les relations génotype/phénotype. Par ailleurs, l'analyse des mutations faux-sens CCP et DRK montrait que la mutation CCP avait un effet plus délétère sur la fonction de IFT52 que celle de DRK, confirmant leur pathogénicité et expliquant le phénotype squelettique du cas CCP. Toutefois, cela n'expliquait pas la variabilité du phénotype rénal observée parmi les individus. De fait, nous avons considéré une deuxième mutation homozygote faux-sens présente dans le cas DRK dans le gène UBE2C, codant une enzyme E2 de conjugaison d'ubiquitine impliquée dans la sortie de mitose. La modélisation de la structure 3D de la protéine a montré que la mutation affectait la liaison à l'ubiquitine et de fait, probablement la fonction de la protéine. Des études in vitro ont confirmé que la mutation ralentissait la sortie de mitose des cellules. Par ailleurs, afin d'étudier l'impact de la mutation sur le développement rénal, une souris portant la mutation DRK (knock-in) a été générée par CRISPR/Cas9. Bien que les souris Ube2cKI/KI présentent un défaut de croissance et une létalité précoce similaire au modèle knock-out, validant ainsi la pathogénicité de la mutation, les reins sont normaux chez ces animaux. Nous avons donc émis l'hypothèse que le phénotype rénal résultait de la synergie entre les mutations IFT52 et UBE2C. Afin de tester cette hypothèse, des études de synergie ont été réalisées chez le poisson zèbre, par injection de morpholino ift52 dans des embryons issus du croisement d'animaux ube2c+/-. Cette approche n'a malheureusement pas permis d'induire un défaut rénal chez les embryons ube2c-/-. Ainsi soit le cas DRK présente une autre mutation pouvant expliquer le phénotype rénal, soit les modèles animaux (souris, poisson zèbre) ne sont pas appropriés à l'étude de l'implication de UBE2C dans le développement rénal humain. De manière inattendue, l'étude de IFT52 a permis de mettre en évidence un espacement anormal des centrioles composant le centrosome des cellules Ift52-/-. La cohésion du centrosome est maintenue par deux mécanismes : le lien protéique entre les parties proximales des centrioles, et la force des microtubules (MTs) qui s'exerce sur le centrosome. Aucune altération des principaux composants du lien protéique, notamment c-Nap1 et rootletine, n'a pu être observée dans les cellules Ift52-/-. En revanche, nous avons montré que Ift52 interagissait et co-localisait partiellement avec centrine au niveau de la partie distale du centrosome, suggérant un rôle de IFT52 dans le mécanisme des MTs. En effet, nous avons montré que les MTs présentaient un défaut d'ancrage au centrosome et qu'ils étaient moins dynamiques dans les cellules Ift52-/-. Nos résultats démontrent un rôle extra-ciliaire de IFT52 dans l'ancrage des MTs et la cohésion du centrosome, à la manière de son partenaire IFT88 au niveau des MTs mitotiques, ajoutant un autre mécanisme physiopathologique aux ciliopathies associées à IFT52Ciliopathies are multisystemic disorders due to mutations in genes encoding proteins localizing at the cilium. Cilia are microtubule-based organelles present at the surface of almost all vertebrate cells. IFT52 is a key component of the intraflagellar transport IFT-B complex that guarantees cilium formation and functions. Missense, nonsense mutations and in-frame deletions have been identified in IFT52 in three families presenting distinct phenotypes of ciliopathies: multicystic kidney dysplasia (MCKD) or skeletal dysplasia such as short ribs-polydactyly (SRP) or Sensenbrenner (SB). To understand the phenotype variability, we sought to characterize the pathogenicity of the mutations by using patient fibroblasts and CRISPR/Cas9-induced cellular and animal models. First, we showed that the nature of the in-frame (SRP) and nonsense mutations (SB) actually led to a frameshift and an in- frame exon skipping, respectively that partially explained the genotype/phenotype correlation. On the contrary, analyses of missense mutations from SRP and MCDK cases indicated that SRP mutation had a more severe impact on IFT52 function than the DRK mutation, confirming the pathogenicity of the mutations and explaining the skeletal defects of SRP case. However, it did not explain the renal phenotype variability observed amongst the individuals. Thus, we considered a second homozygous missense mutation in the MCDK case in UBE2C, a gene encoding an ubiquitin conjugating enzyme involved in metaphase/anaphase transition. Tridimensionnal modelisation of the protein structure showed that the mutation affected the binding with ubiquitin and likely the function of the protein. In vitro studies confirmed that the mutation delayed mitosis exit. In order to study the role of Ube2c in kidney development, a knock-in (KI) mouse line of the patient mutation was generated by CRISPR/Cas9 technique. Although Ube2cKI/KI failed to thrive and died early, similarly to the knock-out line, kidneys appeared normal in these animals. So we hypothesized thet the renal phenotype of the MCDK case could come from a synergy between the mutations in IFT52 and UBE2C. To test this hypothesis, we performed synergy experiments by injecting ift52 morpholino in zebrafish embryos issued from ube2c+/- incrosses, but we did not observe kideny defects in ube2c-/- embryos. Thus, we conclude that either the MCDK individual present another mutation responsible for the renal phenotype or the animal models we used (mouse, zebrafish) were not appropriate to study the involvement of UBE2C in human kidney development. Surprisingly, the study on IFT52 mutations highlighted an abnormal splitting of the centrioles of the same centrosome in Ift52-/- cells. Centrosome cohesion is guaranteed by two mechanisms: a protein linker between proximal parts of the centrioles and the microtubule (MTs) forces exerted on the centrosome. The proteins from the protein linker, such as c-Nap1 and Rootletin, did not seem to be affected by the loss of Ift52. However, we showed that Ift52 interacted and partially co-localized with centrin at the distal part of the centriole, suggesting a role for Ift52 in the MTs mechanism. Indeed, we showed that in Ift52-/- cells, MTs presented failed to anchor at the centrosome and their dynamic was reduced. These defects could be the cause of the centrosome splitting and suggest an extra-ciliary role for IFT52 in MTs anchoring and centrosome cohesion, as its partner IFT88 in mitosis, adding another physiopathological mechanism to the IFT52-associated ciliopathies
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Jia, Zhongtao [Verfasser], Nicolaus von [Gutachter] Wirén, Klaus [Gutachter] Humbeck, and Malcolm [Gutachter] Bennett. "Exploiting natural variation to uncover genes modulating root foraging responses to low nitrogen in Arabidopsis thaliana / Zhongtao Jia ; Gutachter: Nicolaus Wirén, Klaus Humbeck, Malcolm Bennett." Halle (Saale) : Universitäts- und Landesbibliothek Sachsen-Anhalt, 2019. http://d-nb.info/1220288144/34.
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Mastrogiovanni, Gianmarco. "Establishment of new human and mouse liver cancer models and their use to uncover the role of RNF43 and ZNRF3 in liver homeostasis and repair." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/273341.
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Primary liver cancer (PLC) is the second most common cause of cancer death worldwide, preceded only by lung cancer. Current models for PLC either fail to fully recapitulate tumour histology and architecture or are expensive, time consuming and do not allow for personalised drug testing. During the first part of my PhD, I have collaborated with Dr. Laura Broutier in order to established a new 3D in vitro model system for liver cancer. Based on the current knowledge on organoid cultures, we have managed to establish a system to grow primary human liver cancer cells long-term (Broutier et al., in press). Interestingly, the tumour-derived organoids (tumoroids) recapitulate the original tumour histology and genetic alterations and are also able to generate tumours in an in vivo xenograft mouse model after long-term expansion. Furthermore, we have shown that tumoroids can also be successfully used for drug testing, suggesting their use to devise new targeted therapy as well as personalised treatment strategies. Current models to investigate the role of genes in cancer rely mostly on animal studies, which can be very time consuming and cost demanding, especially if resulting in negative outcomes. To overcome this issue, I have set up a protocol for introducing mutations in healthy human liver organoids using the CRISPR-Cas9 technology. Interestingly, after mutating TP53, RNF43 and ZNRF3 either alone or in combination, human organoids undergo genetic alterations and phenotypic changes that partially resemble the ones observed in tumoroids. This data suggests that this system could be used as a screening platform to study gene function before using animal models. In the last part, I have further explored the role of RNF43 and ZNRF3 (R&Z) - two newly identified WNT pathway negative regulators mutated in many cancer types - in the liver using an in vivo mouse model. Interestingly, conditional deletion of R&Z specifically in adult mouse hepatocytes results metabolic changes that eventually lead to extensive liver damage. However, when the liver is challenged to regenerate in a chronic damage model, R&Z mutated livers fail to fully repair and show presence of multiple regenerative nodules. Later, livers develop either focal nodular hyperplasia and/or early hepatocellular carcinoma. These data suggest that R&Z have an important role in both liver metabolic homeostasis and liver regeneration and that their alteration can eventually lead to cancer formation.