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1
Liu, Ruisheng. "Regulatory Functions of the Juxtaglomerular Apparatus." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5199-3/.
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Hamilton, Alexander Brian. "Immune functions & mechanisms of regulatory T cells." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648192.
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Smith, Richard LeRoy. "Cis-regulatory Sequence and Co-regulatory Transcription Factor Functions in ERα-Mediated Transcriptional Repression." BYU ScholarsArchive, 2009. https://scholarsarchive.byu.edu/etd/2261.
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Estrogens exert numerous actions throughout the human body, targeting healthy tissue while also enhancing the proliferative capacity of breast cancers. Estrogen signaling is mediated by the estrogen receptor (ER), which binds DNA and ultimately affects the expression of adjacent genes. Current understanding of ER-mediated transcriptional regulation is mostly limited to genes whose transcript levels increase following estrogen exposure, though recent studies demonstrate that direct down-regulation of estrogen-responsive genes is also a significant feature of ER action. We hypothesized that differences in cis-regulatory DNA was a factor in determining target gene expression and performed computational and experimental studies to test this hypothesis. From our in silico analyses, we show that the binding motifs for certain transcription factors are enriched in cis-regulatory sequences adjacent to repressed target genes compared to induced target genes, including the motif for RUNX1. In silico analyses were tested experimentally using dual luciferase reporter assays, which indicate that several ER binding sites are estrogen responsive. Mutagenesis of transcription factor motifs (for ER and RUNX1) reduced the response of reporter gene. Further experiments demonstrated that co-recruitment of ER and RUNX1 is necessary for repression of gene expression at some target genes. These findings highlight a novel interaction between ER and RUNX1 and their role in transcriptional repression in breast cancer.
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Fristedt, Rikard. "Regulatory Functions of Protein Phosphorylation in Plant Photosynthetic Membranes." Doctoral thesis, Linköpings universitet, Cellbiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-62303.
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Oxygenic photosynthesis is the process in plants, algae and cyanobacteria which converts light energy from the sun into carbohydrates and at the same time produces oxygen from water. Both carbohydrates and oxygen are essential to sustain life on earth. Sunlight is thus a necessity for life, but it can also cause severe problems for photosynthetic organisms, which have evolved several remarkable acclimation systems to cope with light fluctuations in the environment. In higher plants the light driven reactions of photosynthesis proceed in the chloroplast thylakoid membranes highly organized into stacked regions of grana and interconnecting stroma lamellae. The grana structure is thought to provide functional benefits in the processes of acclimation of the photosynthetic apparatus, particularly in the quality control of photosystem II (PSII) were photodamaged PSII is repaired in a stepwise manner. These processes in the thylakoid membranes were suggested to be regulated by reversible phosphorylation of several proteins in PSII and in its light harvesting antennae complexes (LHCII). Two thylakoid protein kinases, called STN8 and STN7, have been previously identified as responsible for the phosphorylation of PSII and LHCII, respectively. However, molecular mechanisms and the exact functions of these protein phosphorylation events remained largely unknown. In this thesis research I have demonstrated that the PSII protein phosphorylation is needed for the maintenance of the thylakoid structure in Arabidopsis thaliana chloroplasts. A big part of the work on characterization of proteins and their phosphorylation has been done using novel mass spectrometry techniques, and we further developed a label-free method for quantitative studies of protein phosphorylation. The phosphorylation of PSII proteins was found to be diurnal regulated and required for maintenance of the cation-dependent functional stacking of the thylakoid membranes. This phosphorylation was further shown to be important for the regulated turnover of the D1 protein of PSII. Phosphorylation of the plant specific TSP9 protein was found to be dependent on STN7 kinase, and plants deficient in TSP9 showed reduced ability to perform the photosynthetic state transitions and to execute thermal dissipation of excess light energy under high light conditions. I also accomplished characterization of the protein phosphorylation in thylakoids from Arabidopsis plants subjected to high light treatment and discovered STN7-dependent phosphorylation of the antenna protein CP29 required for the adaptive disassembly of PSII supercomplexes in conditions of high light stress.
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Yang, Pei-Jung. "Regulatory functions during the transition to new school environments." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609242.
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Salerno, Paolo. "«Energy Regulatory Commission»: Character and functions after energy reform." Pontificia Universidad Católica del Perú, 2016. http://repositorio.pucp.edu.pe/index/handle/123456789/115445.
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The Mexican energy reform in December 2013 has represented a radical change in the structure of the sector, which has grown from a public monopoly to a competitive market. This article aims to analyze the attributions and the legal and administrative nature which has be granted to the Energy Regulatory Commission (CRE) after the normative change that will play a key role in the correct implementation thereof. The nodal problem is to confirm if the CRE has being given the correct legal instruments to develop its function autonomously and transparently.La reforma energética mexicana de diciembre de 2013 ha representado un cambio radical en la estructuración del sector, el cual ha pasado de ser un monopolio público a un mercado de libre competencia. El presente artículo tiene como objetivo analizar las atribuciones y la naturaleza jurídico administrativa que se ha concedido a la Comisión Reguladora de Energía (CRE) tras el cambio normativo, dado que este, en calidad de organismo regulador del sector, tendrá un rol fundamental en la correcta implementación de la misma. El problema nodal de la cuestión reside en corroborar si se ha dotado a la CRE de los correctos instrumentos jurídicospara desenvolver su función de forma autónoma y transparente.
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Vučićević, Dubravka [Verfasser]. "Diverse regulatory functions of long non-coding RNAs / Dubravka Vučićević." Berlin : Freie Universität Berlin, 2017. http://d-nb.info/1137509899/34.
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Shi, Xinhui. "Regulatory Functions of ZmMYB31 and ZmMYB42 in Maize Phenylpropanoid Pathway." University of Toledo / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1302295047.
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Tilley, Gareth John. "Electrochemical investigations into iron-sulfur cluster containing proteins." Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365300.
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Liu, Chaohong. "Regulatory functions of the actin cytoskeleton in B cell receptor signaling." Thesis, University of Maryland, College Park, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3599621.
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The binding of antigen (Ag) to the B cell receptor (BCR) induces the activation of intracellular signaling and the reorganization of the actin cytoskeleton. However, the function of actin reorganization and the mechanisms by which BCR signaling and actin reorganization is coupled have not been well studied. This thesis has investigated how BCR signaling regulates actin reorganization and how actin remodeling in turn influences BCR signalig. My studies show that the key stimulatory signaling molecule of the BCR, Bruton's tyrosine kinase (Btk), is critical for actin polymerization at the activation surface and BCR clustering and B cell spreading, events that are essential for signaling initiation and amplification. The key inhibitory signaling molecule, SH2-containing phosphatidylinositol-5 phasphatase (SHIP-1), is important for removal of F-actin from the activation surface, and actin-mediated B cell contraction and the formation of BCR central clusters. SHIP-1 suppresses actin polymerization by inhibiting Btk-dependent activation of Wiskott-Aldrich syndrome protein (WASP). These results suggest that BCR signaling can regulate B cell morphology and surface BCR clustering via modulationg actin dynamics. To understand the roles of actin reorganization in BCR signaling, I investigated the effects of gene knockout of the two actin regulators, WASP and its homolog, neuronal (N)-WASP. My results show that both WASP and N-WASP are required for optimal BCR clustering, B cell spreading, and BCR signaling, but they play distinct roles. WASP promotes actin polymerization, B cell spreading, BCR clustering, and signaling amplification, and N-WASP inhibits actin polymerization at the activation surface and promotes B cell contraction, BCR central cluster formation, and signaling attenuation. Importantly, B cell-specific N-WASP knockout causes increases in the levels of autoantibody. In addition, WASP and N-WASP negatively regulate each other, compete for Arp2/3, and are inversely regulated by Btk and SHIP-1. Taken together, these results demonstrate that the balance of stimulatory and inhibitory BCR signaling controls actin dynamics and organization through regulating the activities of WASP and N-WASP. Actin remodeling in turn amplifies BCR signaling activation or down regulation by modulating B cell morphlogy and the organization of surface BCRs.This research reveals a bidrectional feedback loop between BCR signaling and the actin cytoskeleton.
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Yalamanchili, Hari Krishna. "Computational approaches for protein functions and gene association networks." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206477.
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Entire molecular biology revolves primarily around proteins and genes (DNA and RNA). They collaborate with each other facilitating various biomolecular systems. Thus, to comprehend any biological phenomenon from very basic cell division to most complex cancer, it is fundamental to decode the functional dynamics of proteins and genes. Recently, computational approaches are being widely used to supplement traditional experimental approaches. However, each automated approach has its own advantages and limitations. In this thesis, major shortcomings of existing computational approaches are identified and alternative fast yet precise methods are proposed.
First, a strong need for reliable automated protein function prediction is identified. Almost half of protein functional interpretations are enigmatic. Lack of universal functional vocabulary further elevates the problem. NRProF, a novel neural response based method is proposed for protein functional annotation. Neural response algorithm simulates human brain in classifying images; the same is applied here for classifying proteins. Considering Gene Ontology (GO) hierarchical structure as background, NRProF classifies a protein of interest to a specific GO category and thus assigns the corresponding function.
Having established reliable protein functional annotations, protein and gene collaborations are studied next. Interactions amongst transcription factors (TFs) and transcription factor binding sites (TFBSs) are fundamental for gene regulation and are highly specific, even in evolution background. To explain this binding specificity a Co-Evo (co-evolutionary) relationship is hypothesized. Pearson correlation and Mutual Information (MI) metrics are used to validate the hypothesis. Residue level MI is used to infer specific binding residues of TFs and corresponding TFBSs, assisting a thorough understanding of gene regulatory mechanism and aid targeted gene therapies.
After comprehending TF and TFBS associations, interplay between genes is abstracted as Gene Regulatory Networks. Several methods using expression correlations are proposed to infer gene networks. However, most of them ignore the embedded dynamic delay induced by complex molecular interactions and other riotous cellular mechanisms, involved in gene regulation. The delay is rather obvious in high frequency time series expression data. DDGni, a novel network inference strategy is proposed by adopting gapped smith-waterman algorithm. Gaps attune expression delays and local alignment unveils short regulatory windows, which traditional methods overlook.
In addition to gene level expression data, recent studies demonstrated the merits of exon-level RNA-Seq data in profiling splice variants and constructing gene networks. However, the large number of exons versus small sample size limits their practical application. SpliceNet, a novel method based on Large Dimensional Trace is proposed to infer isoform specific co-expression networks from exon-level RNA-Seq data. It provides a more comprehensive picture to our understanding of complex diseases by inferring network rewiring between normal and diseased samples at isoform resolution. It can be applied to any exon level RNA-Seq data and exon array data.
In summary, this thesis first identifies major shortcomings of existing computational approaches to functional association of proteins and genes, and develops several tools viz. NRProF, Co-Evo, DDGni and SpliceNet. Collectively, they offer a comprehensive picture of the biomolecular system under study.published_or_final_version
Biochemistry
Doctoral
Doctor of Philosophy
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Nabhan, Joseph. "Regulatory functions of proteasome component RPN11POH1 in Schistosoma mansoni and human cells." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111843.
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The 26S proteasome is the principal degradation structure of intracellular proteins in eukaryotes. The proteasome is composed of two 19S regulatory particles and a 20S catalytic core. The lid region of the 19S proteasome comprises at least 8 subunits that recognizes proteasomal substrates, including misfolded, truncated, or erroneously posttranslated proteins, as well as other tightly controlled and short-lived proteins. Such substrates are typically tagged with a small peptide called ubiquitin to facilitate their rapid and efficient recognition and translocation to the proteasome. The objective of this study was to characterize the Schistosoma mansoni and human homologues of proteasomal lid subunit POH1/RPN11. Earlier reports had suggested that overexpression of the fission yeast padl homologue can influence the activity of an AP1-like transcription factor. We showed that SmPOH, the Schistosoma mansoni homologue, stabilizes AP1 transcription factor c-Jun both in vitro and in cultured mammalian cells. We also demonstrated a dose-dependent SmPOH-induced stabilization of c-Jun in vitro. In contrast, SmPOH did not stabilize another well-known proteasomal substrate, p53, in vitro. Others later demonstrated that yeast POH1/RPN11 is a divalent cation-dependent metalloprotease deubiquitinase and outlined a conserved catalytic motif termed JAMM/MPN+ responsible for this activity. To better understand the structure-function relationship of POH1/RPN11 with regard to c-Jun stabilization, we showed that the Cys-120 residue of human POH1 (hPOH1), embedded in the JAMM/MPN+ motif, is required for the stabilizing effect on c-Jun. Furthermore, we established that hPOH1 influences c-Jun stability by altering its state of ubiquitination and intracellular localization. Parallel experiments were conducted to test the effect of hPOH1 on another proteasomal substrate, p27Kip, but no changes could be seen either in its stability or its localization. RNAi experiments targeting SmPOH transcripts in cultured schistosomula resulted in a lethal phenotype, thus illustrating the critical role of SmPOH expression in the parasite. Expression levels of SmPOH were reduced by ∼ 90% following a 9-day incubation with siRNAs targeting the SmPOH sequence. We further performed a survey to examine the expression levels of multiple proteasome subunits in cercaria, schistosomula, and adult stages of Schistosoma mansoni. Our results suggest a pivotal role for the proteasome in the development of the parasite. A better understanding of the function of the proteasome in S. mansoni may lead to the identification of novel drug targets and newer approaches for chemotherapy.
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Wee, Hee-Jun. "Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms." Kyoto University, 2003. http://hdl.handle.net/2433/149370.
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Edalat, Maryam. "Multiple Functions of Glutathione Transferases : A Study on Enzymatic Function, Regulatory Role and Distribution in Mouse and Man." Doctoral thesis, Uppsala University, Department of Biochemistry, 2002. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2152.
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To cope with various endogenous toxin and xenobiotics nature has equipped the organisms with a proper protection system. Glutathione transferases (GSTs) are important components of the cellular defense against oxidative stress. These proteins appear to be suited for different tasks.
Based on catalytic activity of GSTs with monochlorobimane (MCB), a screening method was developed for identification of active GSTs in bacterial colonies and for characterization of combinatorial GST libraries.
Solvent viscosity effects on kcat and kcat/Km on wild-type human GST A1-1 and phenylalanine-220 mutants indicate a physical step being the rate-limiting step in the catalytic mechanism.
Three residues that were under evolutionary selection pressure were identified in Mu class GSTs. By changing these residues in human GSTM2-2, a 1000-fold change of catalytic activity towards GSTM1-1 was accomplished.
Using peptide phage display, a peptide sequence was found that acts as non-substrate ligand for human GST M2-2. The peptide sequence was shown to be highly similar to the C-terminal region of c-Jun N-terminal kinase (JNK). JNK is a kinase linked to activating protein-1 (AP-1) transcriptional activity, which is part of the regulation of cell proliferation and apoptosis in response to cellular stress. Reporter gene assays in cell lines showed that human GST M2-2 coactivates the transcriptional activity of AP-1.
GSTs as part of the cellular defense against oxidative stress could be important in inflammatory processes. The distribution of GSTs in the intestine of both mice and human in abnormal inflammatory state was investigated immunohistochemically. Using an experimental mouse model, it was shown that mouse GST A4-4 is markedly induced while, the expression of Mu and Pi class GSTs is reduced in the colon of conventional and germ-free mice with extensive colitis. Moreover, the expression of mouse GST A4-4 was elevated with time when germ-free mice were exposed to normal bacteria flora. In contrast, Mu and Pi class GSTs showed decreased expression in the colon of germ-free mice associated with commensal flora. The Alpha, Mu and Pi class GST levels in mouse colon were increased when germ-free mice received Lactobacillus strain GG.
The distribution of Alpha, Mu and Pi class GST in the intestinal tissues of patients with Crohn’s disease was investigated using immunohistochemistry. All the three classes were consistently expressed in the intestinal epithelium as well as in macrophage-like cells and smooth muscle tissue. The mucus secreting goblet cells, however, did not express Alpha class GST.
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Murrugarra, Tomairo David M. "Algebraic Methods for Modeling Gene Regulatory Networks." Diss., Virginia Tech, 2012. http://hdl.handle.net/10919/28388.
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So called discrete models have been successfully used in engineering and computational systems biology. This thesis discusses algebraic methods for modeling and analysis of gene regulatory networks within the discrete modeling context. The first chapter gives a background for discrete models and put in context some of the main research problems that have been pursued in this field for the last fifty years. It also outlines the content of each subsequent chapter. The second chapter focuses on the problem of inferring dynamics from the structure (topology) of the network. It also discusses the characterization of the attractor structure of a network when a particular class of functions control the nodes of the network. Chapters~3 and 4 focus on the study of multi-state nested canalyzing functions as biologically inspired functions and the characterization of their dynamics. Chapter 5 focuses on stochastic methods, specifically on the development of a stochastic modeling framework for discrete models. Stochastic discrete modeling is an alternative approach from the well-known mathematical formalizations such as stochastic differential equations and Gillespie algorithm simulations. Within the discrete setting, a framework that incorporates propensity probabilities for activation and degradation is presented. This approach allows a finer analysis of discrete models and provides a natural setup for cell population simulations. Finally, Chapter 6 discusses future research directions inspired by the work presented here.Ph. D.
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Boohaker, Rebecca. "The Dynamic Functions of Bax are Dependent on Key Structural and Regulatory Features." Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5135.
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Bax is an essential mediator of cell fate. Since its discovery in 1985 as a protein that interacts with the anti-apoptotic protein, Bcl-2, key elements related to its function, structure and regulation remains to be determined. To this end, mitochondrial metabolism was examined in non-apoptotic Bax-deficient HCT-116 cells as well as primary hepatocytes from Bax-deficient mice. Although mitochondrial density and mitochondrial DNA content was the same in Bax-containing and Bax -deficient cells, MitoTracker staining patterns differed, suggesting the existence of Bax -dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in Bax -deficient cells, while glycolysis was increased. These results suggest that cells lacking Bax have a deficiency in the ability to generate ATP through cellular respiration, supported by detection of reduced citrate synthase activity in Bax -deficient cells. Expression of either full length or C-terminal truncated Bax in Bax -deficient cells rescued ATP synthesis and oxygen consumption and reduced glycolytic activity, suggesting that this metabolic function of Bax was not dependent upon its C-terminal helix. Expression of BCL-2 in Bax-containing cells resulted in a subsequent loss of ATP measured, implying that, even under non-apoptotic conditions, an antagonistic interaction exists between the two proteins. Bax is composed of nine alpha-helices. While three of these helices have features of a trans-membrane region, the contribution of each domain to the apoptotic or non-apoptotic functions of Bax remains unknown. To examine this, we focused on the C-terminal alpha-9 helix, an amphipathic domain with putative membrane binding properties and discovered that it has an inherent membrane-binding and cytotoxic capacity. A peptide based on the last twenty amino acids (CT20p) of the alpha-9 helix was synthesized and proved a potent inducer of cell death independent of any apoptotic stimuli. The solubility of CT20p allowed it to be encapsulated in polymeric nanoparticles (NPs), and these CT20p-NPs caused the death of colon and breast cancer cells in vitro and induced tumor regression in vivo, using a murine breast cancer tumor model. CT20p caused increased mitochondrial membrane potential followed by cell death via membrane rupture, without the characteristic membrane asymmetry associated with apoptosis. Hence, while CT20p is based on Bax, its innate cytotoxic activity is unlike the parent protein and could be a powerful anti-cancer agent that bypasses drug resistance, can be encapsulated in tumor-targeted nanoparticles and has potential application in combination therapies to activate multiple death pathways in cancer cells. While previous work revealed novel aspects of the biology of Bax that were unrecognized, new structural information is needed to fully elucidate the complexity of Bax's function. One approach is to use computational modeling to assess the solved structure of Bax and provide insight into the structural components involved in the activity of the protein. Use of molecular dynamics simulators such as GROMACS, as well as other computational tools provides a powerful means by which to test the feasibility of certain modifications in defined parameters. Such work revealed that the removal of the C-terminal alpha-9 helix of Bax, which normally resides within a hydrophobic pocket, significantly destabilized the protein, perhaps explaining how the protein transitions from soluble to membrane-bound form and maintain energy production via aerobic respiration or, conversely, how the C-terminus helix conveys cytotoxicity. Collectively, this work reveals that Bax is more than an inducer of cell death but has complex activities yet to be determined.Ph.D.
Doctorate
Molecular Biology and Microbiology
Medicine
Biomedical Sciences
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Rajagopalan, Ramya. "Genomics and regulatory functions of microRNAs and small silencing RNAs in Arabidopsis thaliana." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/43787.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2007.After leaf 151, two journal articles with separate numberings (leaves [69]-79, 565-577).
Includes bibliographical references.
Small RNA-mediated gene silencing is a mechanism widely employed by eukaryotes to repress many loci including some involved in critical developmental transitions. In plants, endogenous small RNAs consist of two broad classes, the ~21-nucleotide (nt) microRNAs (miRNAs) and the diverse ~22-24-nt trans-acting and heterochromatic short interfering RNAs (siRNAs). In order to more extensively characterize the small RNA landscape in plants and to identify undiscovered miRNAs and siRNAs, we performed high-throughput sequencing of small RNAs. We generated a large dataset consisting of >340,000 unique sequences expressed in several representative plant organs and developmental stages including wild-type seedlings, flowers, leaves and siliques. Application of enhanced miRNA annotation criteria gleaned from the data revealed the existence of at least 38 apparently recently-evolved miRNAs that were much less abundant in plant tissues than the 26 conserved miRNA families, and had a greater diversity of predicted target genes. We characterized several of these miRNAs more closely. Our results supported a homeostatic auto-regulatory loop for DCL1 via the intron-embedded miR838, and elaborated on the prevailing model of DCLl-mediated miRNA biogenesis with the finding that at least two miRNAs (miR839 and miR822) are processed exclusively by DCL4. Several microRNA target sites were experimentally validated, including the miR823-directed cleavage of the DNA cytosine methylation factor CHROMOMETHYLASE3. We also identified a trans-acting siRNA-generating locus which we called TAS4, and confirmed that miR828 triggers phased siRNA production by specifying targeted cleavage of TAS4 transcripts.
(cont.) The evolving miRNAs described in this work may have lineage-specific roles, and their discovery potentiates future functional investigation of recently-emerged miRNAs and their evolution in Arabidopsis. Finally, we discovered thousands of endogenous candidate heterochromatic siRNAs of unknown function, the majority of which mapped to unannotated regions of the genome especially prone to generating siRNAs ("hotspots") or to repetitive or transposable elements. Our small RNA study suggests that a significant proportion of the genome is primed for the emergence of new miRNA families or for siRNA production, and expands the roles of these small RNAs in shaping regulatory circuits and transcriptome output.
Ramya Rajagopalan.
Ph.D.
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Chang, Tsun-Kai. "A Novel Autophagy Regulatory Mechanism that Functions During Programmed Cell Death: A Dissertation." eScholarship@UMMS, 2009. http://escholarship.umassmed.edu/gsbs_diss/686.
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Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether the Atg gene regulatory pathway that was defined in yeast is utilized for all autophagy in animals, as well as if autophagy could function in a cell death scenario, are less understood.
The Drosophila larval digestive tissues, such as the midgut of the intestine and the salivary gland, are no longer required for the adult animal and are degraded during the pupal stage of development. Cells stop growing at the end of larval development, and proper cell growth arrest is required for midgut degradation. Ectopic activation of the PI3K/Akt signaling induces cell growth and inhibits autophagy and midgut degradation. Down regulating PI3K/Akt pathway by Pten mis-expression activates autophagy. In addition, mis-expression of autophagy initiator Atg1 inhibits cell growth and knocking down autophagy restore PI3K/Akt activity. Together, these results indicate that autophagy and growth signaling mutually inhibit each other.
Midgut destruction relies on the autophagy gene Atg18, but not caspase activation. The intestine length shortens and the cells undergo programmed cell size reduction, a phenomenon that also requires Atg18, before cell death occurs during midgut destruction. To further investigate whether cell size reduction is cell autonomous and requires other Atg genes, we reduced the function of Atg genes in cell clones using either gene mutations or RNAi knockdowns. Indeed, many Atg genes, including Atg8, are required for autophagy and cell size reduction in a cell autonomous manner. Surprisingly, Atg7 is not required for midgut cell size reduction and autophagy even though this gene is essential for stress-induced autophagy. Therefore, we screened for known E1 enzymes that may function in the midgut, and discovered that Uba1 is required for autophagy, size reduction and clearance of mitochondria. Uba1 does not enzymatically substitute for Atg7, and Ubiquitin phenocopies Uba1, suggesting Uba1 functions through ubiquitination of unidentified molecule(s) to regulate autophagy.
In conclusion, this thesis describes: First, autophagy participates in midgut degradation and cell death. Second it reveals a previously un-defined role of Uba1 in autophagy regulation. Third it shows that the Atg genes are not functionally conserved and the requirement of some Atg genes can be context dependent.
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Msallam, Rasha. "Intravital imaging and immuno-regulatory functions of mast cells in cutaneous immune responses." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05T019.
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La peau est un « avant poste » fascinant du système immunitaire. Elle forme une barrière entre l'environnement extérieur et l’organisme. Elle est aussi le point d'entrée pour les agents pathogènes, contre lesquels le système immunitaire organise des réponses adaptatives. Les acteurs de l'immunité innée de la peau contrôlent l'invasion des pathogènes et perçoivent également des changements environnementaux physiques et chimiques directs. Plusieurs composants du système immunitaire, tels que des cellules dendritiques (DCs), les macrophages (MΦ) et les mastocytes (MCs), participent à l'éradication des pathogènes et à l'initiation des réponses mémoires adaptatives. Ce qui permet une mobilisation rapide des cellules T effectrices ainsi que la sécrétion des anticorps par les cellules B à la suite d’une seconde exposition aux agents pathogènes. Les MCs qui sont des cellules résidentes du derme, jouent un rôle déterminant dans la libération de signaux d’alertes et sont classiquement considérés comme des cellules effectrices de la réaction allergique cutanée liée à l'IgE. Plusieurs observations récentes indiquent que les MCs seraient aussi impliqués dans les processus immunorégulateurs lors de l'initiation des réponses immunitaires adaptatives, dans le maintien de la tolérance périphérique aux composants de la peau et dans la régénération de la peau au cours des processus de cicatrisation. Cependant, les interactions entre les MCs et d'autres cellules immunitaires innées et adaptatives recrutées dans des conditions inflammatoires cutanées n'ont pas été élucidées en détail. Dans ce travail, nous décrivons l'utilisation d'une nouvelle souris possédant des MCs fluorescents (RMB), dans laquelle nous avons marqué les MCs FcεRI+ avec un marqueur fluorescent rouge tomato (TdT) et avec un système d'ablation conditionnelle basé sur l'expression concurrente du récepteur de la toxine diphtérique (DTR). Avec ces souris RMB, nous avons visualisé la dynamique des MCs et nous avons suivi les interactions entre les MCs et les lymphocytes T régulateurs (Tregs) après l'activation des MCs par l'IgE, dans une réaction inflammatoire typique de l'anaphylaxie cutanée passive (PCA). Dans un second volet d’étude, nous avons évalué le rôle des MCs lors d'un modèle expérimental de la greffe de peau de l'oreille, afin de révéler leur influence dans la cinétique de rejet ou prise de greffe du transplant. Nous avons constaté que 1) l'activation et la dégranulation des MCs induites par le pontage du récepteur FcεRI via des IgE couplées à un antigène multivalent sont les seules responsables de la réaction de PCA, et induisent le recrutement de Tregs ayant une grande motilité sur le site de l'inflammation. Nous avons constaté dans ces conditions, que les MCs restent immobiles, et que les Tregs établissent des contacts dynamiques avec les MCs dans le derme. 2) En outre, nous avons mis en place un modèle pour identifier les paramètres moléculaires de l'interaction MC-Treg et avons constaté que le complexe de l'antigène avec l'IgE peut être présenté aux Tregs en association avec les molécules du complexe majeur d'histocompatibilité de classe II, permettant la formation des contacts stables MC-Treg. 3) En utilisant un modèle de transplantation de la peau in vivo, nous avons montré que l'ablation conditionnelle des MCs conduit à une accélération du rejet du greffon dans le cas d'une transplantation en présence d’une disparité d’antigènes d’histocompatibilité mineurs depuis une souris mâle sur une souris femelle. Nous avons également constaté un impact inattendu de l'ablation des MCs dans la greffe de peau en l’absence de disparité antigénique d'une souris femelle sur une souris femelle, conduisant à un rejet rapide. Les MCs semblent donc être essentiels pour la cicatrisation et la régénération tissulaire après greffe. (...)The skin is a fascinating outpost of the immune system. It performs a barrier function between the outside environment and the inner body and is also a port of entry for pathogens against which the immune system mounts adapted responses. The skin innate immune defenses control pathogen invasion and perceive also direct physical and chemical environmental changes. Several component of the immune system such as dendritic cells (DC), macrophages (MΦ) and mast cells (MC) participate in initial pathogen clearance and in initiating adaptive memory responses, allowing rapid mobilization of effector T cells and secretion of B cellderived antibodies after secondary pathogen challenge. MCs residing in the dermis exert a determinant alert function through the liberation of various factors and are classically considered as effector cells in the IgE-mediated cutaneous allergic reaction. As emerging now, MC are also involved in immunoregulatory processes during the initiation of adaptive immune responses, the maintenance of peripheral tolerance to skin components and skin regeneration during wound healing. Yet, the crosstalks between MCs and other innate and adaptive immune cells recruited during cutaneous inflammatory conditions have not been elucidated in detail. Here, we report the use of a novel Mast cell fluorescent reporter mouse (RMB), in which we tagged FcεRI+ MCs, with red fluorescence marker tomato (Tdt) and with a conditional ablation system based on concurrent diphtheria toxin receptor (DTR) expression. Using these RMB mice, we visualized MC dynamics and monitored MC interactions with regulatory T lymphocytes (Tregs) after IgE-mediated activation of MCs, in a typical passive cutaneous anaphylaxis (PCA) inflammatory reaction. Using another setting, we further assessed the role of MC during experimental ear skin grafting to reveal their potential influence in skin grafting and rejection. We found that 1) the activation and degranulation of MCs induced by FcεRI crosslinking by multivalent IgE is solely responsible for the PCA reaction and induces the recruitment of highly motile regulatory T cells (Tregs) to the site of inflammation. In these conditions, we found that MC remain sessile and Tregs establish dynamic contacts with MC in the dermis. 2) Further we set up a model system to reveal the molecular requirement for MC-Treg interaction and found that antigen complexed with IgE were able to be presented to Treg in association with major histocompatibility complex class II molecules allowing the formation of stable MC-Treg contacts. 3) Using in vivo skin transplantation model, we showed that conditional ablation of MCs leads to an acceleration of skin transplant rejection in sex-mismatched model (male skin transplant to female). We also found an unexpected impact of MC conditional ablation in sex-matched skin graft (female skin transplant to female) leading to rapid rejection, implying that MCs are essential for the wound healing reaction and the regeneration of tissue continuity after grafting. The aforementioned results point out to an important immunoregulatory role of MC beyond their classically described activator functions in inflamed tissues. The fact that MC constantly interact with Treg during inflammatory processes suggest that MCs could participate in skin homeostasis by exerting tolerogenic functions. These functions remain to be elucidated at the molecular level as presented in the discussion
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Chang, Tsun-Kai. "A Novel Autophagy Regulatory Mechanism that Functions During Programmed Cell Death: A Dissertation." eScholarship@UMMS, 2013. https://escholarship.umassmed.edu/gsbs_diss/686.
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Autophagy is a cellular process that delivers cytoplasmic materials for degradation by the lysosomes. Autophagy-related (Atg) genes were identified in yeast genetic screens for vehicle formation under stress conditions, and Atg genes are conserved from yeast to human. When cells or animals are under stress, autophagy is induced and Atg8 (LC3 in mammal) is activated by E1 activating enzyme Atg7. Atg8-containing membranes form and surround cargos, close and mature to become the autophagosomes. Autophagosomes fuse with lysosomes, and cargos are degraded by lysosomal enzymes to sustain cell viability. Therefore, autophagy is most frequently considered to function in cell survival. Whether the Atg gene regulatory pathway that was defined in yeast is utilized for all autophagy in animals, as well as if autophagy could function in a cell death scenario, are less understood.
The Drosophila larval digestive tissues, such as the midgut of the intestine and the salivary gland, are no longer required for the adult animal and are degraded during the pupal stage of development. Cells stop growing at the end of larval development, and proper cell growth arrest is required for midgut degradation. Ectopic activation of the PI3K/Akt signaling induces cell growth and inhibits autophagy and midgut degradation. Down regulating PI3K/Akt pathway by Pten mis-expression activates autophagy. In addition, mis-expression of autophagy initiator Atg1 inhibits cell growth and knocking down autophagy restore PI3K/Akt activity. Together, these results indicate that autophagy and growth signaling mutually inhibit each other.
Midgut destruction relies on the autophagy gene Atg18, but not caspase activation. The intestine length shortens and the cells undergo programmed cell size reduction, a phenomenon that also requires Atg18, before cell death occurs during midgut destruction. To further investigate whether cell size reduction is cell autonomous and requires other Atg genes, we reduced the function of Atg genes in cell clones using either gene mutations or RNAi knockdowns. Indeed, many Atg genes, including Atg8, are required for autophagy and cell size reduction in a cell autonomous manner. Surprisingly, Atg7 is not required for midgut cell size reduction and autophagy even though this gene is essential for stress-induced autophagy. Therefore, we screened for known E1 enzymes that may function in the midgut, and discovered that Uba1 is required for autophagy, size reduction and clearance of mitochondria. Uba1 does not enzymatically substitute for Atg7, and Ubiquitin phenocopies Uba1, suggesting Uba1 functions through ubiquitination of unidentified molecule(s) to regulate autophagy.
In conclusion, this thesis describes: First, autophagy participates in midgut degradation and cell death. Second it reveals a previously un-defined role of Uba1 in autophagy regulation. Third it shows that the Atg genes are not functionally conserved and the requirement of some Atg genes can be context dependent.
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Landes, Nico. "Vitamin E : elucidation of the mechanism of side chain degradation and gene regulatory functions." Phd thesis, [S.l. : s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975679473.
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Botts, Ryan T. "Recovery and Analysis of Regulatory Networks from Expression Data Using Sums of Separable Functions." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1275926172.
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Ramdas, Jyoti. "Functions Of Nucleosomes And Other Regulatory Factor(S) In Homologous Recombination Promoted By RecA Protein." Thesis, Indian Institute of Science, 1994. http://hdl.handle.net/2005/99.
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Homologous genetic recombination occurs during the life cycle of virtually every organism Genetic studies especially in prokaryotes and fungi have defined the rules of recombination, led to the characterization of alternate pathways and to the development of molecular models The biochemistry of homologous genetic recombination has advanced most productively in bacteria and fungi due to the extensive genetic understanding of these organisms The identification of mutants defective in homologous recombination, purification and characterization of the gene products that participate in recombination has brought the ultimate goal of reconstituting a cell-k free system for Eschenchia coli, at least with naked DNA substrates, closer to reality.
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Yin, Wenzhe. "Arabidopsis MS1 functions as a hub in the transcriptional regulatory network of late tapetum development." Thesis, University of Nottingham, 2017. http://eprints.nottingham.ac.uk/43214/.
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The development of the pollen grains within the anther locule relies upon the nourishing and secretory properties of a tissue layer termed tapetum. The transition of the post-meiotic phase of tapetum development depends on the MALE STERILITY 1. In the ms1 mutant tapetum development is arrested post-meiosis and lacks subsequent biological processes, such as biosynthesis and secretion of pollen wall/coat components and the tissue programmed cell death process. MS1 exhibits a transient expression pattern, which is tightly regulated and critical for tapetum development and viable pollen formation. Therefore, understanding the genetic control of MS1 is key to uncover the regulation of post-meiotic tapetum development. During this project, three regulation levels of MS1 were studied: (i) transcriptional activation, (ii) auto-repression and (iii) post-translational proteolysis. Phylogenetic footprinting analysis and molecular promoter dissection was used to investigate the transcriptional control of expression and a distal upstream sequence (−2900 to −2066 bp) was found to be essential for the activation of MS1. Three evolutionarily conserved non-coding sequences (CNS), enriched with unusually long consensus motifs, and binding site combinations of MS1 upstream transcription factors (TFs) were found within the −2 kb MS1 upstream sequence. These may serve as essential cis-regulatory elements (CREs) for MS1 expression. ChIP experiments were used to investigate MS1 autorepression; the MS1 protein was shown to bind to the second exon of its genomic locus and to repress its own expression. Post-translational proteolysis was investigated using a triple mutant of the MS1 interacting gene that encodes for an E3 ubiquitin ligase LRB1 and its two paralogs LRB2 and LRB3; which exhibits a novel tapetum phenotype that may be induced by altered removal of MS1 protein in the lrb123 tapetum. The MS1 protein possesses a Plant Homeotic Domain (PHD) finger and belongs to a plant-specific C-terminal PHD contained protein (CPCP) family. Although extensive research has been carried out on the tapetum regulation role of MS1, very little is known about the underlying molecular mechanism. A series in-silico comparative analysis of the CPCP sequences in this thesis found that this family originated from green algae. Besides the PHD, two evolutionarily conserved domains, termed MS1/MMD1 Associated Domain 1 (MAD1) and MAD2, were identified in the protein. Molecular modelling of the MS1 PHD domain predicted a histone reader role with high affinity to H3K4me2/3 histone peptides. Super-resolution STED confocal observation showed that subnuclear localisation of the MS1 protein is distinctive with canonical TFs and aggregates at rounded speckles that resemble Polycomb bodies. A meta-data-analysis of MS1 microarrays found that most MS1 immediately responding genes are repressed by MS1, which is on the contrary to the previously proposed activator role of MS1. MS1 may therefore be a unique plant-specific histone reader family protein that participates in gene repression as a co-repressor. MYB99 has previously been hypothesised to be a direct target of MS1, regulating late tapetum development. Comprehensive phenotyping was carried out on two MYB99 null alleles; however, no defects were identified, probably due to high function redundancy among the MYB family TFs. In addition, no evidence of direct activation by MS1 was observed by yeast one-hybrid and ChIP analysis. Interestingly, a PCD indicator gene was down-regulated in the myb99 mutant, suggesting a tapetal PCD regulatory role for MYB99.
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Aksoy, Ezra. "Regulatory mechanisms in toll-like receptir pathways: control of dendritic cell functions by protein kinases." Doctoral thesis, Universite Libre de Bruxelles, 2005. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210916.
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Muhammad, Nasiruddeen. "Legitimate expectations in investment treaty arbitration : balancing between state's legitimate regulatory functions and investor's legitimate expectations." Thesis, University of Dundee, 2015. https://discovery.dundee.ac.uk/en/studentTheses/2e4fa295-67da-4e0a-b6b2-338a138bccfc.
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One of the impacts of globalization on the nation states across the globe is how the system reduces governmental intervention and weakens governmental control over many activities within a state's territory. From the governance perspective, states regulate and administer affairs within their territories in accordance with their constitutional mandates of satisfying fundamental objectives of their needs; the extent to which states can satisfy those needs is critically dependent on their ability to pursue public interest oriented policies for meeting the basic needs and for further development of its citizens i.e. for the public good. However, as the tasks of states entail regulation and administration for public purpose, it carries the risk of infringement of private interest or unfair treatment against private entities operating within the state. The complex nature of the investor - state relationship, therefore, provides a lush ground for tension and conflict between public and private interests. Private interests in this context, are the state's commitments to the foreign investors covered by investment treaty jurisprudence, while public interests are the domestic needs regarding public good also linked to compliance with other non-investment albeit international obligations. Under various domestic legal orders and some international law regimes, there is a well-developed principle of legitimate expectations which allows courts and domestic tribunals to filter, both, the legitimacy of individual's expectations and public interest dimension of governmental activities. In investment treaty arbitration, however, this tool or mechanism is lacking. The practice of the investment treaty (ad hoc) tribunals reveals the worrying degree of inconsistency and lack of coherence in the analysis of formulation and application of the principle of legitimate expectations. The principle as applied by investment treaty tribunals can be understood as 'reliance by foreign investor' caused by 'a state through its representation, conduct, or established legal framework', pursuant to which the foreign investor suffers damage or loss emanating from the state's regulatory or administrative measure. While Claimants in investment treaty arbitration are increasingly relying on the principle to frame their claims, its contours remain unsettled. In addition to the varying degrees of ambiguity in the formulation of the principle, the reach of its application raises the tension of overlap with a public interest dimension of the state's regulatory and administrative functions, particularly in the areas of human rights, public health, environment, and necessity measures or public choice. This thesis uses the doctrine of 'margin of appreciation' as an analytical framework for a comparative approach methodology. The doctrine of margin of appreciation as a public law tool could serve as a lens through which investment treaty tribunals could both formulate and apply the principle of legitimate expectations without obscuring the regulatory and administrative functions of states.
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Vock, Christina [Verfasser]. "Analysis of gene regulatory functions of the human acyl-CoA-binding-protein in lipid metabolism / Christina Vock." Kiel : Universitätsbibliothek Kiel, 2009. http://d-nb.info/1019810416/34.
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Kuns, Robin E. "Protein 4.1B functions as a putative tumor suppressor with novel growth regulatory activities in the mammary gland." Cincinnati, Ohio : University of Cincinnati, 2005. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1108334486.
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Vahlne, Gustaf. "Natural killer cell inhibitory and activating receptors : regulatory role in effector functions against normal and tumor cells /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-430-3/.
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Gutiérrez, Miranda Laura Adriana [Verfasser], and Marina [Akademischer Betreuer] Schorpp-Kistner. "JUNB regulatory functions in lymphangiogenesis: from mESCs to zebrafish / Laura Adriana Gutiérrez Miranda ; Betreuer: Marina Schorpp-Kistner." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://d-nb.info/1202608000/34.
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KUNS, ROBIN E. "PROTEIN 4.1B FUNCTIONS AS A PUTATIVE TUMOR SUPPRESSOR WITH NOVEL GROWTH REGULATORY ACTIVITIES IN THE MAMMORY GLAND." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1108334486.
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Pyzik, Michal. "TGF-[beta]1 selectively induces Foxp3 transcription factor and regulatory functions in CD4+CD25⁻CD45RBLow T cell population." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101737.
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CD4+ regulatory T (TREG) cells are important contributors to the induction and maintenance of peripheral tolerance. This heterogeneous population consists of naturally occurring and induced CD4 + TREG cells that share between themselves key immunoregulatory characteristics. Their phenotype and function often relies on the expression of Foxp3 transcription factor and the presence of the immunomodulating cytokine TGF-beta1. The inter-dependence between TGF-beta1 and Foxp3 in the induction and maintenance of peripheral tolerance is gradually being elucidated. Thus, we investigated the effects of TGF-beta1 on induction or maintenance of regulatory functions in CD4+CD25- as well as CD4+CD25+ T cells. TGF-beta1 treatment was able, independent from APCs, to promote TREG cell differentiation from non-regulatory CD4+CD25- T cells in a concentration-dependent fashion through Foxp3 induction. Next, we investigated the effect of TGF-beta1 on purely naive CD4+CD25- CD45RBHIGH T cell subset. Fresh or TGF-beta1-treated CD45RBHIGH T cells did not display regulatory functions nor Foxp3 expression. In stark contrast, TGF-beta1 treatment promoted regulatory activity in the CD4 +CD25- CD45RBLOW T cells and enhanced Foxp3 expression. Interestingly, fresh CD45RBLOW cells, albeit expressing noticeable levels of Foxp3 mRNA and protein, were unable to suppress effector T (TEFF) cell proliferation. Furthermore, addition of neutralizing anti-IL-10R Ab completely abrogated this suppression, consistent with the ability of TGF-beta1 treated CD45RBLOW to synthesize IL-10 mRNA upon re-stimulation in vitro. TGF-beta1 treatment or blockade did not lead to preferential growth or enhanced function of naturally-occurring CD4+CD25+ TREG cells, yet it caused a significant increase in Foxp3 expression. Altogether, TGF-beta1 preferentially promotes the induction of IL-10 secreting CD4+ regulatory T cells from CD45RBLOW precursors through Foxp3 induction.
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Wolanski, Julia Caroline [Verfasser], and Ralf [Akademischer Betreuer] Bartenschlager. "Regulatory Functions of the DAP Kinase Family in Antiviral RIG-I Signalling / Julia Caroline Wolanski ; Betreuer: Ralf Bartenschlager." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1178010279/34.
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Xiao, Minfeng, and 肖敏鳳. "The regulatory mechanisms and physiological functions of an outer membrane protein opmpW during anaerobic adaptation in Escherichia coli." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/206531.
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ompW encodes a widespread outer-membrane porin protein in Gram-negative bacteria. It has been implicated in bacterial responses to various antibiotics and environmental substances such as antibiotics, drugs and mouse mucus etc. Little is known, however, about its regulation and physiological roles during bacterial stress responses. Recently, comparative genomics studies revealed that the ompW gene is a core regulon of the global transcription factor FNR (Fumarate Nitrate Reduction) which mediates the transition from aerobic to anaerobic lifestyle of facultative bacteria. Anaerobiosis represents a predominant challenge encountered by many bacteria in their natural ecological niches and human hosts. This thesis thus aims to elucidate the molecular mechanism of FNR-dependent regulation of ompW expression and its relevance to the anaerobic adaption of the model facultative bacterium E. coli. Regulation of ompW expression by several other key physiological signals related to the anaerobiosis of E. coli, as well as the physiological significance, is also explored systematically.
In the first half of the thesis, FNR-dependent regulation of ompW is confirmed by in vivo transcriptional activity assay, and then further confirmed at mRNA and protein level by RT-qPCR and western blotting. EMSA combined with transcriptional activity assay reveals that FNR directly binds with two sites centered at -81.5 and -126.5 bp respectively on ompW promoter (PompW). While binding to the -81.5 site by FNR activates the transcription of ompW, interaction with the -126.5 site represses it, and repression through the -126.5 site is dependent on primary occupancy of the -81.5 site by FNR. Based on these molecular mechanisms, a novel regulatory model of ompW expression during anaerobic adaptation of E. coli is proposed. Growth competition assay further confirmed the physiological significance of this fine-tuned regulation of ompW by FNR in facilitating the fitness and adaptation of E. coli during the transition from aerobic to micro-aerobic and anaerobic lifestyles.
In the second half of the thesis, it is demonstrated that two other physiological signals related to the anaerobiosis of E. coli participate in the regulation of ompW, i.e. carbon and electron sources. The molecular mechanisms of how the relevant transcription factors, namely CRP and NarXL, mediate ompW transcription were elucidated: CRP activates the transcription of ompW by binding with the -42.5 site on PompW when glucose is absent; NarL represses the expression of ompW via its binding with the -18.5 site on PompW in the presence of nitrate (the most preferred electron source of E. coli during anaerobic growth). Fumarate is estimated to enter the central channel of OmpW and rescues OmpW-mediated colicin S4 killing of E. coli, suggesting OmpW is a receptor for fumarate and revealing its role in facilitating C4-dicarboxylates utilization.
In summary, my study reveals a previously unrecognized, highly co-ordinated and dynamic regulation network for the expression of the widely distributed Gram-negative bacterial minor porin protein OmpW. Given the high conservancy of both the ompW gene and its promoter regions in several pathogenic bacterial species, my study contributes to the understanding of the pathogenicity of these species in the host relevant environment of anaerobiosis.published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
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Yung, Mei Hing. "Regulatory functions of two Cis-elements on tissue-specific and wounding responsive activation of Phaseolus vulgaris PAL2 promoter." Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.361483.
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Wolanski, Julia C. [Verfasser], and Ralf [Akademischer Betreuer] Bartenschlager. "Regulatory Functions of the DAP Kinase Family in Antiviral RIG-I Signalling / Julia Caroline Wolanski ; Betreuer: Ralf Bartenschlager." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-235312.
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Vågesjö, Evelina. "Exploring immune cell functions and ways to make use of them." Doctoral thesis, Uppsala universitet, Integrativ Fysiologi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-299683.
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In addition to host defense, alternative functions of immune cells are emerging. Immune cells are crucial during healing of injured tissue, in formation of new blood vessels, angiogenesis, and also in maintaining the balance in inflammation having immune regulating functions. Over the last decade a higher degree of heterogeneity and plasticity of immune cells have been reported and immune cells develop different characteristics in different situations in vivo. This thesis investigates roles for immune cells in situations of muscle hypoxia and reduced blood perfusion, wound healing in skin and at sites of transplantation of allogeneic islets of Langerhans and on top of this, ways to steer immune cell function for future therapeutic purposes. A specific neutrophil subset (CD49d+VEGFR1+CXCR4high) was found to be recruited to VEGF-A released at hypoxia and these neutrophils were crucial for functional angiogenesis. In muscle with restricted blood flow macrophages were detected in perivascular positions and started to express aSMA and PDGFR1b and were found to directly assist in blood flow regulation by iNOS-dependent NO production. This essential function in muscle regain of function could be boosted by plasmid overexpression of CXCL12 where the effect of these macrophages chaperoning the vasculature was amplified improving limb blood flow regulation. The effect on macrophages accelerating tissue regeneration being amplified by CXCL12 was tested in a model of cutaneous wound healing where the administration of CXCL12 was optimized for high bioavailability. In the skin, CXCL12-treatment induced accumulation of TGFb-expressing macrophages close to the wound driving the healing process, and subsequently the wounds healed with an efficiency never reported before. In the last study means to circumvent systemic immune suppressive therapy required in allogeneic transplantation was investigated. Allogeneic islets of Langerhans transplanted to muscle were immediately destroyed by the host immune system. Co-transplanting islets and CCL22-encoding plasmids we could curb this fast rejection for 10 days by accumulating CD4+CD25+FoxP3+ regulatory T lymphocytes at the site for transplantation preventing islet grafts from being attacked by the host cytotoxic T lymphocytes. In summary this thesis outlines distinct immune cell subsets being essential for regain of tissue function in hypoxia, ischemia and post injury and ways to amplify specific immune cell functions in these situations that are feasible for clinical use.
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Ferrer-Dalmau, Falgueras Jofre. "Study of the biological functions of the nonessential regulatory subunits of the protein phosphatase Glc7 in the yeast Saccharomyces cerevisiae." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/130775.
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L’única subunitat catalítica de PP1 en S. cereivisiae, Glc7, interacciona amb un mínim de 31 subunitats reguladores que li permeten regular tot el ventall de funcions. En aquesta tesis, hem estudiat les soques delecionades per cadascuna de les 21 subunitats reguladores no essencials de Glc7 realitzant-ne tant l’anàlisi fenotípic com transcripcional. Aquest estudi a gran escala ens ha permès determinar nous fenotips i perfils transcripcionals desconeguts, a més, ens ha permès focalitzar en dues subunitats reguladores: Ref2 i Reg1.
En aquesta tesi, demostrem que Ref2, una subunitat reguladora necessària pel processament i maduració dels mRNA i/o dels snoRNAs, és necessària pel correcte funcionament de la homeòstasis iònica. Les cèl·lules delecionades per REF2 presenten un fenotip de sensibilitat a cations que és depenent de la unió de Glc7 implicant una nova funció del complex Glc7-Ref2. Ref2 forma part del complex holo-CPF (Cleavage Poly(A)denylation Factor), on la majoria de components són essencials per la supervivència cel·lular. Per aquesta raó, es van estudiar cèl·lules que contenien al·lels termo-sensibles dels components del holo-CPF a temperatures semi-restrictives ens ha permès determinar que aquest complex no està involucrat en la l’homeòstasi iònica. Malgrat aquesta funció separada entre el complex holo-CPF i Ref2, mutants en ambdós presenta sensibilitat a agents d’estrès en la integritat de la paret cel·lular. Tant la deleció de REF2 com els mutants en els components de la via de la integritat de la paret cel·lular presenten una sensibilitat additiva implicant una sinèrgia en l’adaptació a agents estressors de la paret cel·lular.
Les cèl·lules ref2 presenten una aneuploïdia, implicant una duplicació en diversos cromosomes, amb una duplicació en el cromosoma XII comuna en el fons genètic BY4741. Aquesta aneuploïdia és deguda a la no unió de Glc7 en el holo-CPF. Diploides homozigots delecionats pel gen REF2 no són capaços d’esporular, possiblement per una mala segregació dels cromosomes en la meiosi, perquè aquestes cèl·lules no són defectives en els primers passos de la meiosi.
L’altre fenotip estudiat en el mutant ref2 és la resposta a proteïnes mal plegades (UPR). Les cèl·lules ref2 són tolerants a tunicamicina possiblement degut a l’aneuploïdia. L’estudi evolutiu d’una soca salvatge al llarg de 120 generacions amb la presència continua de tunicamicina va demostrar que com a primer pas adaptatiu implica la duplicació del cromosoma II i; la resposta a llarg termini implica la pèrdua de la duplicació en el cromosoma II i la inducció específica de certs gens, entre ells les bombes de resistència a drogues pleiotròpiques.
Reg1, la subunitat reguladora de Glc7 implicada en la regulació negativa dels gens repressor de glucosa defosforilant Snf1, presenta un fenotip de sensibilitat a agents que provoquen l’acumulació de proteïnes mal plegades, com la tunicamicina. Aquest fenotip coincideix amb l’al·lel glc7-109, que no permet la unió de les subunitats reguladores a Glc7, relacionant l’UPR i la regulació de la cinasa Ire1. Els nostres resultats indiquen que tant la hiperactivació de Snf1 com la sobreexpressió de proteïnes SNf1 constitutivament hiperactivades en el mutant reg1 inclús incrementen la seva sensibilitat a tunicamicina. Finalment, l’anàlisi dels mutants en els components de la via Snf1 ens ha permès determinar que la falta de RIM101 provoca una sensibilitat a tunicamicina, possiblement a la impossibilitat d’expressió de PMR1, una bomba d’alta afinitat necessària pel transport de Ca2+/Mn2+ al Golgi essencial per la UPR.
En resum, els nostres resultats ens han permès descriure noves funcions per Ref2, incloent l’homeòstasi iònica i la regulació de la integritat de la paret cel·lular. Per l’altre costat, hem destapat una nova funció de Reg1 en la regulació a proteïnes mal plegades.The only catalytic subunit of PP1 in S. cereivisiae, Glc7, interacts with at least 31 regulatory subunits that regulate the myriad of Glc7 functions. Among those subunits we performed in this thesis both transcriptional and phenotypic analysis of 21 yeast strains lacking one of the non-essential regulatory subunit of Glc7. With these high-throughput technologies we have determined theirs transcriptional profiles and new phenotypes which allowed us to focus on two regulatory subunits: Ref2 and Reg1. We demonstrate in this thesis that Ref2, a regulatory subunit necessary for the processing and maturation of mRNA and/or snoRNAs is also required for the proper functioning of ionic homeostasis under conditions of cation stress. Cells lacking REF2 display hypersensitivity to cation stress which is dependent on the binding to Glc7 involving a new function of the complex Glc7-Ref2. Ref2 is integrated in the holo-CPF (Cleavage Poly(A)denylation factor), where most components are essential for cell survival. For this reason, the study of cells carrying thermo-sensitive alleles of the holo-CPF components in semi-restrictive temperatures allowed us to conclude that this complex is not involved in ionic homeostasis. Despite this unrelated function between holo-CPF and Ref2, the holo-CPF mutants display sensitivity to cell wall stressors agents, as ref2 cells do. Deletions of REF2 and mutants in components of the cell wall integrity pathway have synergistic effects under cell wall stressors. Cells lacking REF2 display an aneuploidy, implying duplication of chromosomes, being the chromosome XII duplicated in all analysed cases of the BY4741 genetic background. This aneuploidy is due to the inability of Glc7 to bind to the holo-CPF. Furthermore, homozygous diploids lacking the REF2 genes are unable to sporulate, possibly due to a chromosome missegregation in meiosis, since cells are not defective in the early events of meiosis. Another phenotype studied in ref2 cells was the unfolded protein response (UPR). ref2 cells are hypertolerant to tunicamycin, possible due to its aneuploidy. The evolutionary study of a wild-type strain grown in tunicamycin for 120 generations showed, as an early adaptive step, duplication of chromosome II. Long-term adaptive step involves the loss of the chromosome duplication and the specific induction of certain genes, including those involved in the pleiotropic drug resistance phenomenon. Reg1, the Glc7 subunit involved in the negative regulation of glucose-repressible genes by dephosphorylating Snf1 kinase, displays hypersensitivity to agents that trigger the accumulation of unfolded proteins, such as tunicamycin. This phenotype is shared by the glc7-109, which prevents the binding of the regulatory subunits to Glc7, linking the UPR to a possible regulation of the Ire1 kinase. Our results indicate that hyperactivation of Snf1 or overexpression of constitutively activated Snf1 in reg1 mutant cells even increases the sensitivity to tunicamycin. Finally, the analysis of mutants of the components of the Snf1 pathway allowed us to conclude that the lack of RIM101 causes sensitivity to tunicamycin, possibly due to the impossibility of expressing PMR1, a high affinity Ca2+/Mn2+ P-type ATPase required for Ca2+ and Mn2+ transport into Golgi and essential for UPR. In summary, results of this thesis allow us to describe new functions for Ref2, including the ionic homeostasis and regulation of the cell wall integrity. On the other hand, we have uncovered that Reg1 is required for the correct response to unfolded proteins.
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Taylor, Ewan R. "The role of DNA damage proteins and signaling pathways in the regulatory functions of the Human Papillomavirus 16 E2 protein." Thesis, University of Glasgow, 2003. http://theses.gla.ac.uk/30727/.
Full textAbstract:
Human papillomavirus type 16 (HPVI6) is a causative agent of cervical cancer. The HPV16 viral transcription/replication factor E2 is essential for the viral life cycle. The function of E2 is dependenton the interaction with cellular partner proteins. The amino- terminal domain of E2 is an acidic protein-protein interaction domain essential for all of the functions of E2. A yeast-2-hybrid screen using the amino-terminal domain of HPV16 E2 as bait identified multiple possible partner proteins for E2 function (Boner & Morgan 2002) including the DNA replication/repair protein TopBPl. E2 molecules from HPVI6 and HPV18 interact with multiple proteins involved in the cellular response to DNA damage (e.g. p53, BRCAl, PARP and TopBPl). The role of TopBPl in E2 function and the functional response of E2 to DNA damage stimuli were investigated. Overexpression of TopBPl enhances the transcription and replication activation functions of E2. Overexpression of an amino-terminal truncation mutant of TopBPl has no effect on the transcription/replication functions of E2. During this study a novel method for the detection of E1/E2 DNA replication function by real-time PCR was developed. The UVB irradiation of cells resulted in the significant reduction of both E2 transactivation function and E2 protein amount. These results demonstrated that E2 function is altered by cellular DNA damage response proteins and signaling pathways. In many HPV induced cancers the HPV genome is either present integrated into the cellular chromosomes or is maintained episomally with large DNA deletions/rearrangements. Therefore HPV genome stability is a significant risk factor for the development of HPV induced cancer. Thus the fidelity of DNA replication activated by the HPV 16 E1/E2 replication factors was investigated on undamaged and UVC damaged templates in a variety of genetic backgrounds. On undamaged DNA templates there were a significant amount of mutations due to DNA deletions/rearrangements and the frequency of mutation increased when the template was damaged. This increase on damaged templates was marked in cells with defects in key DNA replication or repair proteins. These results highlight the instability of HPV16 genome replication. The interaction of E2 with DNA damage response proteins and the reduction of E2 function in response to DNA damage may be an evolutionary response by the virus to ensure genetic integrity and host cell viability.
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Dang, Phuong-Nga. "Determining the functions of transcriptional regulatory genes of the npd gene cluster encoding 2,4,6-trinitrophenol degradation in Rhodococcus opacus HL PM-1." [S.l. : s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972630740.
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Zhang, Wan [Verfasser], and Thomas [Akademischer Betreuer] Rausch. "Regulatory functions of two R2R3-MYB transcriptional repressors in Miscanthus phenylpropanoid pathway: Impact on the lignification process / Wan Zhang ; Betreuer: Thomas Rausch." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://d-nb.info/1206416734/34.
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Nga, Dang Phuong. "Determining the functions of transcriptional regulatory genes of the npd gene cluster encoding 2,4,6-trinitrophenol degradation in Rhodococcus opacus HL PM-1." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11482096.
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Tsujikawa, Hiroshi. "Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system." Kyoto University, 2004. http://hdl.handle.net/2433/145275.
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Svensson, Mats. "Evolution of a family of plant genes with regulatory functions in development; studies on Picea abies and Lycopodium annotinum." Doctoral thesis, Uppsala universitet, Institutionen för evolutionsbiologi, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1194.
Full textAbstract:
This work is focused on the molecular genetic basis for morphological change in evolution. Genes belonging to the MADS-box gene family, which includes members, that determine angiosperm floral organ identity, were isolated and characterised from two non-angiosperm plants; Norway spruce (Picea abies) and the club moss (Lycopodium annotinum). The exon/intron organisation of the isolated genes was determined, and its significance as an independent test of the position of a gene within the gene family tree evaluatad. identity genes were identified. One Norway spruce gene, DAL2, is an ortholog to Norway spruce genes that are closely related to the angiosperm floral organ angiosperm C-class MADS-box genes that specify stamen and carpel identity. The expression of DAL2 in male and female cones suggests that orthologous genes in conifers and argiosperms determine the identities of pollen- and seed-bearing structures. Constitutive expression of DAL2 in the angiosperm Arabidopsis resulted in homeotic conversions very similar to those resulting from constiutive expression of the Arabidopsis C-class gene. Angiosperm B-class MADS-box genes determine petal and stamen identity. The isolated Norway spruce B-class orthologs: DAL11, DAL12, and DAL13 are expressed in the developing male cones exclusively, suggesting a conserved function of B-class related genes in the determination of pollen forming organs among seed plants. No orthologs to the floral organ identity genes couId be isolated from the club moss, suggesting that the origin of these gene classes may be coupled to the origin of the pollen and the seed. The club moss MADS-box genes, LAMB2, LAMB4 and LAMB6, conform structurally to plant type MADS-box genes, whereas LAMB1 is divergent in details. The genes LAMB3 and LAMB5 encode shorter proteins. LAMB1 expression is restricted to reproductive structures, whereas LAMB2, LAMB4, LAMB5 and LAMB6 are broadly expressed. The implications from these expression patterns on the ancestral function of plant type MADS-box genes are discussed.
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Jin, Hong [Verfasser], and Manfred [Akademischer Betreuer] Frasch. "Systematic analysis of regulatory functions of genomic fragments identified by immunoprecipitations of Tinman-bound chromatin from Drosophila embryos / Hong Jin. Betreuer: Manfred Frasch." Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/1028958714/34.
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Huang, Liang. "Functions and Regulatory Mechanisms of the Rel Family Transcription Factors, Dorsal and Dif, and the UBC9 Family SUMO Conjugase, Lesswright, in DrosophilaHematopoiesis." Ohio : Ohio University, 2006. http://www.ohiolink.edu/etd/view.cgi?ohiou1162613472.
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Alam, Majid A. "Investigation of regulatory functions of micrornas in skin and hair follicle development and cycling. A role of microRNA-214 in skin and hair follicle homeostasis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/6481.
Full textAbstract:
miRNAs are important post-transcriptional regulators of gene expression which
play vital roles in the arrays of physiological processes, including skin and hair
follicle (HF) development. In this study, the role for miR-214 in the skin and HF
development and their postnatal physiological regeneration was investigated.
miR-214 exhibits discrete expression patterns in the epidermis and HF in
developing and postnatal skin, and is highly expressed in the epithelial stem
cells and their lineage-committed progenies. The effects of miR-214 on HF
morphogenesis and cycle progression were evaluated by using doxycyclineinducible
miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte
specific miR-214 overexpression during skin embryogenesis resulted in the
partial inhibition of HF induction and formation of the HF reduced in size
producing thinner hair. Overexpression of miR-214 in telogen skin caused
retardation of the anagen progression and HF growth. Inhibitory effects of miR-
214 on HF development and cycling were associated with supressed activity of
stem cells, reduced proliferation in the hair matrix, and altered differentiation.
miR-214 induced complex changes in gene expression programs in
keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and
several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas -catenin acts as a novel conserved miR-214 target. Indeed, the
inhibitory effects of miR-214 on HF development were rescued by
intracutaneous delivery of pharmacological Wnt activator.
Thus, this study demonstrated that by targeting -catenin and, therefore,
interfering with Wnt signalling activity miR-214 may act as one of the upstream
effectors of the signalling cascades which govern HF morphogenesis and
cycling.
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Alam, Majid Ali. "Investigation of regulatory functions of microRNAs in skin and hair follicle development and cycling : a role of microRNA-214 in skin and hair follicle homeostasis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/6481.
Full textAbstract:
miRNAs are important post-transcriptional regulators of gene expression which play vital roles in the arrays of physiological processes, including skin and hair follicle (HF) development. In this study, the role for miR-214 in the skin and HF development and their postnatal physiological regeneration was investigated. miR-214 exhibits discrete expression patterns in the epidermis and HF in developing and postnatal skin, and is highly expressed in the epithelial stem cells and their lineage-committed progenies. The effects of miR-214 on HF morphogenesis and cycle progression were evaluated by using doxycyclineinducible miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte specific miR-214 overexpression during skin embryogenesis resulted in the partial inhibition of HF induction and formation of the HF reduced in size producing thinner hair. Overexpression of miR-214 in telogen skin caused retardation of the anagen progression and HF growth. Inhibitory effects of miR- 214 on HF development and cycling were associated with supressed activity of stem cells, reduced proliferation in the hair matrix, and altered differentiation. miR-214 induced complex changes in gene expression programs in keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas β-catenin acts as a novel conserved miR-214 target. Indeed, the inhibitory effects of miR-214 on HF development were rescued by intracutaneous delivery of pharmacological Wnt activator. Thus, this study demonstrated that by targeting β-catenin and, therefore, interfering with Wnt signalling activity miR-214 may act as one of the upstream effectors of the signalling cascades which govern HF morphogenesis and cycling.
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WEHMER, CARL MARTIN. "THE ROLE OF METROLOGY AND METROLOGY-RELATED FUNCTIONS IN THE REGULATION OF THE FREE MOVEMENT OF GOODS: CONSIDERATIONS ON THE REVISION OF THE EUROPEAN REGULATORY FRAMEWORK." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2009. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=15704@1.
Full textAbstract:
COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIORA presente dissertação de mestrado tem como objetivo analisar, à luz das funções da infraestrutura tecnológica, as proposições do novo marco regulatório europeu para a livre circulação de produtos no mercado comum. Mais especificamente responder à questão formulada pela pesquisa: conseguirá esse novo marco regulatório equacionar e mitigar as deficiências do modelo anterior? Tendo em vista a atualidade do tema, o trabalho discute a importância da metrologia, da normalização, da acreditação e da avaliação da conformidade na eficiência da fiscalização do mercado em nível global e a relevância técnica e econômica que resultam desses processos. No campo institucional, a motivação pelo tema se deu pelo compromisso do Programa de Pós-Graduação em Metrologia de contribuir para o avanço do conhecimento sobre a regulação de mercados e de explorar o tema como oportunidade de fortalecer a ponte em temas da metrologia com a cidadania. No que concerne a metodologia, a pesquisa desenvolveu-se de forma estruturada segundo as seguintes fases complementares: (i) pesquisa bibliográfica e documental dos textos legais e regulamentos europeus aplicáveis; (ii) pesquisa de campo (iii) construção e aplicação do instrumento da pesquisa (questionário) junto a especialistas atuantes nas funções da infraestrutura tecnológica para a qualidade. Consubstanciando os propósitos da pesquisa de mestrado, o trabalho explicitou os resultados mais relevantes consolidados pelo amplo e participativo processo de revisão da legislação européia para a livre circulação de produtos e disponibilizou uma metodologia de avaliação. Finalmente, como conclusão, o trabalho definiu os determinantes da revisão do marco regulatório europeu à luz das mudanças de critérios de aplicação das funções da infraestrutura tecnológica.
The aim of this M.Sc. dissertation is to analyze the New Regulatory Framework for the free movement of goods in the European market, in the light of the functions of the national quality infrastructure. More specifically, to answer the question posed by the study: will the New (and recently revised) Regulatory Framework be able to mitigate the shortcomings of the previous model? Moreover, the study discusses the significance of metrology, standardization, conformity assessment and accreditation for the effectiveness of market surveillance at a global level and the economic and technical relevance of these processes. The commitment of the Postgraduate Metrology Program (Metrology for Quality and Innovation) to contribute to the improvement of technical regulation, while bridging metrology to citizenship, reflect the motivation of this work. The methodology included: (i) a review of the specialized literature (e.g.: legal documentation and applicable European regulation); (ii) a field research and (iii) the development and application of the structured questionnaire to experts in functions of the quality infrastructure and European legislation. The study highlights the most relevant results of the thorough revision of the European regulation for the free movement of goods. It also provided a methodology of assessment for related issues. In tune with the precepts of the Postgraduate Metrology Programme committed to participate in the debate of current topics in metrology and related matters, the dissertation made available to Brazilian legislators lessons learnt by the European Union on the building of a common market. In conclusion, an experience particularly valuable to those committed to make MERCOSUR a successful undertaking. An endeavor of great proportions where goods, services, capital and labor can circulate freely providing the foundation for prosperity.
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Teferi, Desset A. "Role of civil society organisations in the realisation of human rights in Africa and the effect of regulatory mechanisms on their functions : Ethiopia and Ghana perspective." Diss., University of Pretoria, 2011. http://hdl.handle.net/2263/16793.
Full textAbstract:
It is generally acknowledged that development is impossible in the absence of true democracy, respect for human rights, peace and good governance1
Good governance and human rights are mutually reinforcing. In turn, ‘good governance and good public administration are essential aspects of democracy and for achieving democracy a freely functioning, well organised, vibrant and responsible civil society is indispensable.’Democracy presupposes free elections, functioning political parties, independent media and active civil society organisations (CSOs) that can operate freely.4 Human rights are better promoted and protected in a democratic system.5 Accordingly it is submitted that a measure taken by a government which undermines key elements and role players of such a system tends to undermine the protection and promotion of human rights.Thesis (LLM (Human Rights and Democratisation in Africa)) -- University of Pretoria, 2010.
A dissertation submitted to the Faculty of Law University of Pretoria, in partial fulfilment of the requirements for the degree Masters of Law (LLM in Human Rights and Democratisation in Africa). Prepared under the supervision of Mrs. Christina Dowuona-Hammond at the Faculty of Law, University of Leyon, Ghana. 2010.
http://www.chr.up.ac.za/
Centre for Human Rights
LLM