Academic literature on the topic 'Mouse Derived Transcription Factors'
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Journal articles on the topic "Mouse Derived Transcription Factors"
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Maeda, K., M. Nakashima, S. Komori, and T. Watanabe. "Trans-acting regulatory factors for T cell antigen receptor alpha- and gamma-chain gene expression." Journal of Immunology 140, no. 8 (1988): 2796–801. http://dx.doi.org/10.4049/jimmunol.140.8.2796.
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Abstract BALB/c mouse thymoma-derived T cell line, CAK4.4 (Thy-1+, L3T4-, Lyt-2-), produced a large amount of TCR-gamma mRNA, a trace amount of TCR-beta mRNA but no detectable level of TCR-alpha mRNA. Another BALB/c mouse thymoma-derived T cell line, CAK1.3 (Thy-1+, L3T4+, Lyt-2+), synthesized a high level of TCR-alpha as well as TCR-beta mRNA but did not produce any amount of TCR-gamma mRNA. HAT-sensitive clones were established from the two T cell lines. Azaguanine-resistant, HPRT- CAK4.4 cells and bromodeoxyuridine-resistant, TK- CAK1.3 cells were fused by electrofusion method and the resultant hybrids were analyzed for expression of TCR genes as well as the changes of their cell surface phenotypes. Transcription of TCR-gamma gene was completely suppressed in all hybrids tested, although Southern blot analysis showed that the hybrids maintained TCR-gamma chain genes derived from both parental cells. TCR-alpha gene transcription occurred normally in one hybrid. In two other hybrids, TCR-alpha gene transcription was strongly suppressed. Treatment of the hybrid cells with 12-O-tetradecanoyl phorbol-13-acetate reversed the suppression of TCR-alpha gene transcription, but TCR-gamma gene transcription was not recovered by the same treatment. However, transcription level of TCR-beta gene was not changed in all hybrids. Our results suggested that the different trans-acting regulatory mechanisms control the transcription levels of TCR-alpha and TCR-gamma genes and that such a transcriptional control may play a crucial role in the determination of orderly appearance of TCR-gamma and TCR-alpha gene products during T cell ontogeny in the thymus.
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Costa, Robert H., Vladimir V. Kalinichenko, and Lorena Lim. "Transcription factors in mouse lung development and function." American Journal of Physiology-Lung Cellular and Molecular Physiology 280, no. 5 (2001): L823—L838. http://dx.doi.org/10.1152/ajplung.2001.280.5.l823.
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Development of the mouse lung initiates on day 9.5postcoitum from the laryngotracheal groove and involves mesenchymal-epithelial interactions, in particular, those between the splanchnic mesoderm and epithelial cells (derived from foregut endoderm) that induce cellular proliferation, migration, and differentiation, resulting in branching morphogenesis. This developmental process mediates formation of the pulmonary bronchiole tree and integrates a terminal alveolar region with an extensive endothelial capillary bed, which facilitates efficient gas exchange with the circulatory system. The major function of the mesenchymal-epithelial signaling is to potentiate the activity or expression of cell type-specific transcription factors in the developing lung, which, in turn, cooperatively bind to distinct promoter regions and activate target gene expression. In this review, we focus on the role of transcription factors in lung morphogenesis and the maintenance of differentiated gene expression. These lung transcription factors include forkhead box A2 [also known as hepatocyte nuclear factor (HNF)-3β], HNF-3/forkhead homolog (HFH)-8 [also known as FoxF1 or forkhead-related activator-1], HNF-3/forkhead homolog-4 (also known as FoxJ1), thyroid transcription factor-1 (Nkx2.1), and homeodomain box A5 transcription factors, the zinc finger Gli (mouse homologs of the Drosophila cubitus interruptus) and GATA transcription factors, and the basic helix-loop-helix Pod1 transcription factor. We summarize the phenotypes of transgenic and knockout mouse models, which define important functions of these transcription factors in cellular differentiation and lung branching morphogenesis.
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Gray, Paul A. "Transcription factors and the genetic organization of brain stem respiratory neurons." Journal of Applied Physiology 104, no. 5 (2008): 1513–21. http://dx.doi.org/10.1152/japplphysiol.01383.2007.
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Breathing is a genetically determined behavior generated by neurons in the brain stem. Transcription factors, in part, determine the basic developmental identity of neurons, but the relationships between these genes and the neural populations generating and modulating respiration are unclear. The diversity of brain stem populations has been proposed to result from a combinatorial code of transcription factor expression corresponding to the anterior-posterior (A-P) and dorsal-ventral (D-V) location of a neuron's birth. I provide a schematic of transcription factor coding identifying at least 15 genetically distinct D-V subdivisions of brain stem neurons that, combined with A-P patterning, may provide a genetic organization of the brain stem in general, with the eventual goal of describing respiratory populations in particular. Using a combination of fate mapping in transgenic mouse lines and immunohistochemistry, we confirm the parabrachial nuclei are derived from a subset of Atoh1 expression progenitor neurons. I hypothesize the Kölliker-Fuse nucleus can be uniquely defined in the neonate mouse by the coexpression of the transcription factor FoxP2 in Atoh1-derived neurons of rhombomere 1.
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Kaarbø, Mari, Denis I. Crane, and Wayne G. Murrell. "RhoA Regulation of Cardiomyocyte Differentiation." Scientific World Journal 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/491546.
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Earlier findings from our laboratory implicated RhoA in heart developmental processes. To investigate factors that potentially regulate RhoA expression, RhoA gene organisation and promoter activity were analysed. Comparative analysis indicated strict conservation of both gene organisation and coding sequence of the chick, mouse, and human RhoA genes. Bioinformatics analysis of the derived promoter region of mouse RhoA identified putative consensus sequence binding sites for several transcription factors involved in heart formation and organogenesis generally. Using luciferase reporter assays, RhoA promoter activity was shown to increase in mouse-derived P19CL6 cells that were induced to differentiate into cardiomyocytes. Overexpression of a dominant negative mutant of mouse RhoA (mRhoAN19) blocked this cardiomyocyte differentiation of P19CL6 cells and led to the accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiacα-actin. Taken together, these findings indicate a fundamental role for RhoA in the differentiation of cardiomyocytes.
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Boucher, DM, and RA Pedersen. "Induction and differentiation of extra-embryonic mesoderm in the mouse." Reproduction, Fertility and Development 8, no. 4 (1996): 765. http://dx.doi.org/10.1071/rd9960765.
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Extra-embryonic mesoderm, derived at the time of gastrulation from the primitive streak, gives rise to several tissues that function to provide the embryo with nutrients, a means of waste disposal, and mechanical protection. Little is known about the differentiation of this tissue and about the growth and transcription factors involved. The present review focussed on growth and transcription factors that may be involved in differentiation of extra-embryonic mesoderm, and results from fate-mapping and transplantation studies. Methods in vitro available for assaying the effects of growth and transcription factors on development of extra-embryonic development are also discussed.
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Maeda, Yutaka, Vrushank Davé, and Jeffrey A. Whitsett. "Transcriptional Control of Lung Morphogenesis." Physiological Reviews 87, no. 1 (2007): 219–44. http://dx.doi.org/10.1152/physrev.00028.2006.
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The vertebrate lung consists of multiple cell types that are derived primarily from endodermal and mesodermal compartments of the early embryo. The process of pulmonary organogenesis requires the generation of precise signaling centers that are linked to transcriptional programs that, in turn, regulate cell numbers, differentiation, and behavior, as branching morphogenesis and alveolarization proceed. This review summarizes knowledge regarding the expression and proposed roles of transcription factors influencing lung formation and function with particular focus on knowledge derived from the study of the mouse. A group of transcription factors active in the endodermally derived cells of the developing lung tubules, including thyroid transcription factor-1 (TTF-1), β-catenin, Forkhead orthologs (FOX), GATA, SOX, and ETS family members are required for normal lung morphogenesis and function. In contrast, a group of distinct proteins, including FOXF1, POD1, GLI, and HOX family members, play important roles in the developing lung mesenchyme, from which pulmonary vessels and bronchial smooth muscle develop. Lung formation is dependent on reciprocal signaling among cells of both endodermal and mesenchymal compartments that instruct transcriptional processes mediating lung formation and adaptation to breathing after birth.
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Song, Shuang, Chun Cao, Mohamed-Amin Choukrallah, et al. "OBF1 and Oct factors control the germinal center transcriptional program." Blood 137, no. 21 (2021): 2920–34. http://dx.doi.org/10.1182/blood.2020010175.
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Abstract OBF1 is a specific coactivator of the POU family transcription factors OCT1 and OCT2. OBF1 and OCT2 are B cell–specific and indispensable for germinal center (GC) formation, but their mechanism of action is unclear. Here, we show by chromatin immunoprecipitation-sequencing that OBF1 extensively colocalizes with OCT1 and OCT2. We found that these factors also often colocalize with transcription factors of the ETS family. Furthermore, we showed that OBF1, OCT2, and OCT1 bind widely to the promoters or enhancers of genes involved in GC formation in mouse and human GC B cells. Short hairpin RNA knockdown experiments demonstrated that OCT1, OCT2, and OBF1 regulate each other and are essential for proliferation of GC-derived lymphoma cell lines. OBF1 downregulation disrupts the GC transcriptional program: genes involved in GC maintenance, such as BCL6, are downregulated, whereas genes related to exit from the GC program, such as IRF4, are upregulated. Ectopic expression of BCL6 does not restore the proliferation of GC-derived lymphoma cells depleted of OBF1 unless IRF4 is also depleted, indicating that OBF1 controls an essential regulatory node in GC differentiation.
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Woodward, J. G., K. W. Omer, and P. M. Stuart. "MHC class II transcription in different mouse cell types. Differential requirement for protein synthesis between B cells and macrophages." Journal of Immunology 142, no. 11 (1989): 4062–69. http://dx.doi.org/10.4049/jimmunol.142.11.4062.
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Abstract Although the MHC class II genes are known to be regulated transcriptionally, the relative rates of transcription of the four classical class II genes in different cell types have not been investigated. Using nuclear transcriptional analysis, we have investigated the transcriptional rates of the class II genes in the macrophage cell line WEHI-3, normal bone marrow-derived macrophages, L-929 cells, and two different B cell lymphoma lines. Kinetic analysis of class II transcription in IFN-gamma-treated WEHI-3 cells revealed a 4-h delay, followed by a rapid increase in transcription over the next 20 h. A significant basal level of class II transcription, apparent in bone marrow derived macrophages, was also further enhanced by IFN-gamma treatment. None of the class II genes were transcribed in L cells, whereas all class II genes were transcribed constitutively in the B cell lines. In both B cell lines and macrophages, the four class II genes were found to be transcribed at different rates from one another, but the only gene showing a consistent pattern in multiple experiments was A-alpha, always showing the highest rate. We also investigated the effect of protein synthesis inhibition on class II transcription. Cycloheximide treatment of WEHI-3 cells did not inhibit IFN-gamma-induced transcription of the class II genes within 8 h, suggesting that IFN-gamma acts on pre-existing trans-acting factors, rather than inducing their synthesis. In contrast, treatment of B cells with cycloheximide for 8 h significantly reduced class II transcription, suggesting that, in B cells, continuous synthesis of a labile trans-acting factor is required for constitutive expression. These data support the notion that class II expression in B cells is mediated by trans-acting factors distinct from those found in macrophages.
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Almendral, J. M., D. Sommer, H. Macdonald-Bravo, J. Burckhardt, J. Perera, and R. Bravo. "Complexity of the early genetic response to growth factors in mouse fibroblasts." Molecular and Cellular Biology 8, no. 5 (1988): 2140–48. http://dx.doi.org/10.1128/mcb.8.5.2140-2148.1988.
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Genes whose expression is growth factor regulated are likely to be important components in the mechanisms controlling cell proliferation and differentiation. With the aim of identifying some of those genes, a lambda cDNA library was prepared with poly(A)+ RNA from quiescent NIH 3T3 cells stimulated with serum for 4 h in the presence of cycloheximide. Differential screening of approximately 200,000 recombinant phage plaques revealed 2,540 clones that cross hybridized preferentially with [32P]cDNA derived from RNA of stimulated cells rather than with cDNA derived from nonstimulated cells. Cross hybridization of these clones identified 82 independent sequences, including c-fos and c-myc. Seventy-one clones were further studied. Analysis of the changes in transcription and mRNA levels after serum stimulation demonstrated that the kinetics and extent of the induction vary dramatically between the different genes. Cycloheximide in all cases superinduced the mRNA levels by two mechanisms, inhibiting the shutoff of transcription and prolonging the half-lives of the mRNAs. Our results showed that induction of proliferation is accompanied by the onset of a complex genetic program.
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Almendral, J. M., D. Sommer, H. Macdonald-Bravo, J. Burckhardt, J. Perera, and R. Bravo. "Complexity of the early genetic response to growth factors in mouse fibroblasts." Molecular and Cellular Biology 8, no. 5 (1988): 2140–48. http://dx.doi.org/10.1128/mcb.8.5.2140.
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Genes whose expression is growth factor regulated are likely to be important components in the mechanisms controlling cell proliferation and differentiation. With the aim of identifying some of those genes, a lambda cDNA library was prepared with poly(A)+ RNA from quiescent NIH 3T3 cells stimulated with serum for 4 h in the presence of cycloheximide. Differential screening of approximately 200,000 recombinant phage plaques revealed 2,540 clones that cross hybridized preferentially with [32P]cDNA derived from RNA of stimulated cells rather than with cDNA derived from nonstimulated cells. Cross hybridization of these clones identified 82 independent sequences, including c-fos and c-myc. Seventy-one clones were further studied. Analysis of the changes in transcription and mRNA levels after serum stimulation demonstrated that the kinetics and extent of the induction vary dramatically between the different genes. Cycloheximide in all cases superinduced the mRNA levels by two mechanisms, inhibiting the shutoff of transcription and prolonging the half-lives of the mRNAs. Our results showed that induction of proliferation is accompanied by the onset of a complex genetic program.
Dissertations / Theses on the topic "Mouse Derived Transcription Factors"
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Britz, Olivier. "Role of proneural bHLH transcription factors in mouse telencephalic development." Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13170.
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Le cerveau des mammifères est constitué de complexes réseaux de neurones associés à deux types de cellules gliales, les astrocytes et les oligodendrocytes. C'est une structure finement organisée dont la formation repose sur la production et le positionnement correct du nombre approprié des divers types cellulaires au cours du développement. Les progéniteurs indifférenciés s'engagent d'abord dans un lignage cellulaire puis se différencient en un sous-type spécifique de cellule. Cette maturation est liée à des changements précis dans l'expression génique, et récemment les facteurs de transcription de type bHLH Mash1 et Ngns ont été impliqués dans le contrôle de la neurogenèse. La surexpression de ces gènes appelés proneuraux induit la formation de neurones, et l'analyse de mutants a montré leur importance pour la génération de précurseurs neuronaux. Mes travaux de thèse ont aidé à démontrer que les gènes proneuraux jouent un rôle dans la sélection du destin cellulaire chez l'embryon, en favorisant la génération de neurones et en inhibant le destin astrocytaire. De plus, des fonctions de ces gènes sont conservées post-natalement, stade où Mash1 est aussi important pour la formation de neurones et, par ailleurs, est impliqué dans l'oligodendrogenèse. Nous avons également prouvé l'importance de ces gènes pour la spécification de l'identité des neurones corticaux ; en particulier les gènes Ngns sont requis pour spécifier les caractéristiques corticales, glutamatergique et de couche, et répriment simultanément un devenir sous-cortical. Une autre étude a permis d'identifier plusieurs facteurs activés en aval des Ngns dont l'analyse aidera à la compréhension des voies génétiques cruciales pour la corticogenèse. Finalement je présente des travaux en cours sur l'hétérogénéité des précurseurs corticaux et le rôle des gènes proneuraux dans la maturation des précurseurs, la régulation du cycle cellulaire et la spécification neuronale à différents stades du développement<br>The mammalian brain consists of a network of neurons supported by two functionally distinct glial cell types: astrocytes and oligodendrocytes. The formation of this highly organized structure depends on the production and correct placement of the appropriate number and types of cells during development. Undifferentiated progenitor cells are first committed to a particular lineage, followed by terminal differentiation into a specific phenotype. This maturation relies on specific changes in gene expression and recent findings show that neurogenesis is controlled to a large degree by basic helix-loop-helix transcription factors. Overexpression of the proneural bHLH genes Mash1 and Ngns induces panneuronal markers expression and loss-of-function studies showed their requirement for the generation of neuronal precursors. My PhD work helped to demonstrate that proneural genes are major players in programming fate commitment of embryonic multipotent progenitors, thereby promoting neuronal formation while at the same time inhibiting astrogenesis. Furthermore, we showed that some of the functions of these genes are conserved in the postnatal telencephalon where Mash1 also promotes neuron formation, and moreover is required for oligodendrocyte production. Next, we demonstrated that proneural genes contribute to the specification of cortical neuronal identity, and specifically that Ngns are required to specify the cortical, glutamatergic and laminar characters of early-born neurons, while simultaneously repressing an alternative subcortical, GABAergic phenotype. Another study identified several new components of the differentiation cascade(s) activated downstream of Ngns whose analysis will help to understand the genetic pathways fundamental to corticogenesis. Finally I present ongoing studies on the heterogeneity of cortical progenitors and the roles of proneural genes in lineage progression, cell cycle regulation and fate specification at various stages of development
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Yuan, Yuan, and 袁媛. "Transcriptional regulation of mouse secretin receptor in hypothalamic cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47752932.
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As a neuropeptide, both secretin and secretin receptor are expressed in the central nervous system (CNS). It has been revealed that the activities of secretin on hypothalamic cells of rodents are important for osmoregulation and food intake. In the present study, embryonic mouse hypothalamic cell line N42 was used to study the promoter activity of mouse secretin receptor (mSR). By 5′ deletion analysis, a promoter element was identified within ?282 to ?443, relative to the ATG codon, and it contains a GC-box (-297 to -286), a ras responsive element (RRE) (-289 to -276) and an E-box (-416 to -411). Electrophoretic mobility shift assay (EMSA) and supershift analyses showed that Sp1 interacted with the GC-box, another zinc finger
As a neuropeptide, both secretin and secretin receptor are expressed in the central nervous system (CNS). It has been revealed that the activities of secretin on hypothalamic cells of rodents are important for osmoregulation and food intake. In the present study, embryonic mouse hypothalamic cell line N42 was used to study the promoter activity of mouse secretin receptor (mSR). By 5′ deletion analysis, a promoter element was identified within ?282 to ?443, relative to the ATG codon, and it contains a GC-box (-297 to -286), a ras responsive element (RRE) (-289 to -276) and an E-box (-416 to -411). Electrophoretic mobility shift assay (EMSA) and supershift analyses showed that Sp1 interacted with the GC-box, another zinc finger<br>published_or_final_version<br>Biological Sciences<br>Doctoral<br>Doctor of Philosophy
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Nakaki, Fumio. "Induction of mouse germ-cell fate by transcription factors in vitro." Kyoto University, 2014. http://hdl.handle.net/2433/188684.
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Kotova, Irina. "Purification of general RNA polymerase II transcription factors from mouse for studies of proliferation-specific transcription." Doctoral thesis, Umeå : Department of Medical BIochemistry and Biophysics, Umeå University, 2003. http://publications.uu.se/umu/theses/abstract.xsql?dbid=91.
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Stoddart, Neil Richard. "A possible role for embryo-derived factors during mouse preimplantation development?" Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295921.
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Erickson, Drew Talyn. "Multiple Roles for the Transcription Factors Sox6 and Jumonji in Mouse Hematopoiesis." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/195728.
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Sox6, a member of the Sox transcription factor family, is essential for the silencing of epsilon-y-globin gene expression in definitive erythropoiesis of mice and humans. Homozygous Sox6 null mice are neonatal lethal, precluding analysis at later stages. We created adult mice that are deficient in Sox6 specifically in hematopoietic tissues, by transplanting embryonic liver stem cells from Sox6-deficient mice into lethally-irradiated congenic wild-type adult mice. The mice receiving mutant stem cells (mutant-engrafted) showed high expression levels of epsilon-y in bone marrow, spleen and circulating blood compared to mice receiving wild-type and heterozygous stem cells (control-engrafted). The level of expression of epsilon-y in circulating blood was directly correlated with the percentage of successful mutant donor cell engraftment. Additionally, the mutant-engrafted adult mice showed an increase in erythroid precursor cells in bone marrow, spleen and blood. Thus, Sox6 continues to function as a major regulator of epsilon-y in adult definitive erythropoiesis and is required for normal erythrocyte maturation. Moreover, Sox6 may provide a novel therapeutic target by reactivating epsilon-y in patients with hemoglobinopathies such as sickle cell anemia and beta-thalassemia.We have also identified another transcription factor, jumonji, as a downstream target of Sox6. Jumonji is a crtitical transcription factor in neural, cardiac and erythroid development. We report here that jumonji is over-expressed in the fetal liver of Sox6-deficient mice (p100H/p100H). Transfection assays in H2.35 cells reveal that a ~1.6-kb genomic fragment, including the 5' UTR of jumonji, contains both promoter activity and Sox6-mediated repression. Chromatin immunoprecipitation and electromobility shift assays demonstrate that Sox6 binds to a region within the second exon of jumonji. Further transfection analyses confirm that one of five putative binding sites for Sox6 in this region is required for the majority of Sox6-mediated transcriptional repression. In irradiated mice engrafted with Sox6-deficient hematopoietic stem cells, jumonji expression levels are significantly elevated in blood and bone marrow. These results demonstrate that Sox6 plays a major role in the direct repression of jumonji transcription, and it is likely that jumonji plays a cell-autonomous role in the subsequent hematopoietic cell phenotype seen in Sox6-deficient mice.
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Hlatshwayo, Nkosikhona Rejoyce. "Comparison of protein binding microarray derived and ChIP-seq derived transcription factor binding DNA motifs." Thesis, Rhodes University, 2015. http://hdl.handle.net/10962/d1017907.
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Transcription factors (TFs) are biologically important proteins that interact with transcription machinery and bind DNA regulatory sequences to regulate gene expression by modulating the synthesis of the messenger RNA. The regulatory sequences comprise of short conserved regions of a specific length called motifs . TFs have very diverse roles in different cells and play a very significant role in development. TFs have been associated with carcinogenesis in various tissue types, as well as developmental and hormone response disorders. They may be responsible for the regulation of oncogenes and can be oncogenic. Consequently, understanding TF binding and knowing the motifs to which they bind is worthy of attention and research focus. Various projects have made the study of TF binding their main focus; nevertheless, much about TF binding remains confounding. Chromatin immunoprecipitation in conjunction with deep sequencing (ChIP-seq) techniques are a popular method used to investigate DNA-TF interactions in vivo. This procedure is followed by motif discovery and motif enrichment analysis using relevant tools. Protein Binding Microarrays (PBMs) are an in vitro method for investigating DNA-TF interactions. We use a motif enrichment analysis tools (CentriMo and AME) and an empirical quality assessment tool (Area under the ROC curve) to investigate which method yields motifs that are a true representation of in vivo binding. Motif enrichment analysis: On average, ChIP-seq derived motifs from the JASPAR Core database outperformed PBM derived ones from the UniPROBE mouse database. However, the performance of motifs derived using these two methods is not much different from each other when using CentriMo and AME. The E-values from Motif enrichment analysis were not too different from each other or 0. CentriMo showed that in 35 cases JASPAR Core ChIP-seq derived motifs outperformed UniPROBE mouse PBM derived motifs, while it was only in 11 cases that PBM derived motifs outperformed ChIP-seq derived motifs. AME showed that in 18 cases JASPAR Core ChIP-seq derived motifs did better, while only it was only in 3 cases that UniPROBE motifs outperformed ChIP-seq derived motifs. We could not distinguish the performance in 25 cases. Empirical quality assessment: Area under the ROC curve values computations followed by a two-sided t-test showed that there is no significant difference in the average performances of the motifs from the two databases (with 95% confidence, mean of differences=0.0088125 p-value= 0.4874, DF=47) .
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Chao, Christina Seng. "The roles of Nkx2.2 in determination of mouse islet cell fates /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Cell & Developmental Biology) -- University of Colorado Denver, 2007.<br>Typescript. Includes bibliographical references (leaves 144-158). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Geng, Yuhong, and 耿雨紅. "Functional studies of SOX9 in mouse development." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31243071.
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Ho, Siu-yin Bryan, and 何兆賢. "Genetic analyses of the roles of Sox2 and Sox18 in mouse hair development and growth." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206748.
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The mouse pelage hair consists of three types of hair coined primary (guard), secondary (awls and auchenes) and tertiary (zigzag) hair. They display distinct morphologies and are induced consecutively during hair morphogenesis. Previously two identified regulatory mouse mutants, Yellow submarine (Ysb) and Light coat and circling (Lcc) which the chromosomal rearrangements have disrupted the cis-acting regulatory elements of Sox2; resulting in the loss of Sox2 expression in the inner ear. The mutants displayed lighter hair coat color due to a reduction in the proportion of secondary hair and increased proportion of tertiary hair. Sox18 null mutants display darker coat colour and reduced proportion of zigzag hair. To dissect the underlying mechanisms of the phenotypes in hair type specification in 〖Sox2〗^Ysb and 〖Sox2 〗^Lcc mutants and the role of Sox2 and Sox18 in regulating the process; the expression of Sox2 in the hair follicle and the change in the density of hair types in mutants were analyzed.
I have identified the expression pattern of Sox2 in the dermal papilla (DP) of the hair follicle and verified its down-regulation in 〖Sox2〗^Ysband 〖Sox2 〗^Lcc mutants. The DP at the base of hair follicle is the signaling center for the regulation of hair development. Sox2 is specifically expressed in the DP of primary and secondary but not in tertiary hair while Sox18 is expressed in the DP of all hair types. Analysis of Sox2 mutants showed that the number of secondary hair was normal at induction but was reduced and accompanied by an increase in tertiary hair in adult mice. The number of tertiary hair was reduced in Sox18 null mutants. To gain insight into the molecular basis of hair type specification and potential targets of Sox2 in the regulation, gene expression profile in DP cells of 〖Sox2 〗^(EGFP/+)and 〖Sox2 〗^(EGFP/Ysb) mice was examined; the data suggests that genes in the Wnt and BMP signalling pathway were down-regulated in Sox2 mutants; while Runx3 and Corin may act downstream of Sox2 in regulating hair type specification and pigmentation.
Hair follicles enter cycles of growth and regression throughout life during the hair cycle. Sox2 was only expressed in the growth phase while Sox18 was persistently expressed throughout the hair cycle. I further asked if Sox2 and Sox18 regulate post-natal hair development by analysing the expression pattern of Sox2 and Sox18 in wildtype mice and mutants throughout the hair cycle and the progression of hair growth in the mutants. The growth phase of the first hair cycle was extended in Sox2 mutants while the hair cycle in Sox18 null mutants was normal. Cell proliferation was compromised during hair regeneration leading to a delay in hair regeneration in Sox2 mutants.
Sox2 and Sox18 showed overlapping expression in the DP and both regulate hair type specification. To test if Sox2 and Sox18 synergistically regulate hair development, the 〖Sox2〗^(Ysb/Ysb);〖Sox18〗^(-/-) mutants have been generated. Hair morphogenesis and differentiation were impaired; while the number of tertiary hair was increased with reduced number of secondary hair, which phenocopied that of Sox2 mutants. In conclusion, the results suggest that Sox2 and Sox18 functions synergistically on the regulation of hair growth and differentiation.<br>published_or_final_version<br>Biochemistry<br>Doctoral<br>Doctor of Philosophy
Books on the topic "Mouse Derived Transcription Factors"
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Partanen, Maija Elina. Expression of the transcriptional cofactors/histone acetyltransferases CBP and p300 during mouse development and their functional interactions with Gli transcription factors. 2001.
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Hamner, Steve. Characterization of growth of mouse mammary cell lines in collagen gel matrix and modulation of growth by cell-derived diffusible factors. 1985.
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Razzoli, Maria, Alessandro Bartolomucci, and Valeria Carola. Gene-by-Environment Mouse Models for Mood Disorders. Edited by Turhan Canli. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.013.
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Much of the impact of genes on mood disorders likely depends on interactions between genes and the environment. Recent studies demonstrating an interaction between specific genes and life stressful events (early and/or adult) in the modulation of several mood disorders (e.g., serotonin transporter and brain-derived neurotrophic factor genes) have compelled researchers to incorporate information about adverse environmental experiences into the study of genetic risk factors; these same gene-by-environment (G×E) interactions have been identified in mouse models. Notably, G×E not yet described in humans (e.g., serotonin 1A receptor gene) have been uncovered, providing helpful indications to discover similar interactions in humans. Accurate knowledge of the modality of expression of gene-by-stress interaction may help design prevention protocols aimed at identifying susceptibility to mood disorders on the basis of genetic predisposition and exposure to environmental stressful conditions, thus providing patients with appropriate pharmacological and psychological support.
Book chapters on the topic "Mouse Derived Transcription Factors"
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Cardozo, Christopher P. "Identification of Transcription Factor-Binding Sites in the Mouse FOXO1 Promoter." In FOXO Transcription Factors. Springer New York, 2018. http://dx.doi.org/10.1007/978-1-4939-8900-3_3.
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Deatly, Anne M., Ashley T. Haase, and Melvyn J. Ball. "Herpes Simplex Virus Type 1 Transcription during Latent Infections of Mouse and Man." In Psychiatry and Biological Factors. Springer US, 1991. http://dx.doi.org/10.1007/978-1-4684-5811-4_25.
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Scarno, Gianluca, Giuseppe Pietropaolo, Chiara Di Censo, Giovanna Peruzzi, and Giuseppe Sciumè. "Assessing Phosphorylation of STAT Transcription Factors in Mouse Innate Lymphoid Cells." In Methods in Molecular Biology. Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0338-3_6.
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Schaapveld, Roel, Jan Schepens, Frank Oerlemans, Michel Streuli, Bé Wieringa, and Wiljan Hendriks. "Gene Targeting of the Receptor-Like Protein Tyrosine Phosphatase Lar by Homologous Recombination in Mouse Embryonic Stem Cells." In Signalling Mechanisms — from Transcription Factors to Oxidative Stress. Springer Berlin Heidelberg, 1995. http://dx.doi.org/10.1007/978-3-642-79675-3_29.
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Schnapp, Andreas, Horst Rosenbauer, and Ingrid Grummt. "Trans-acting factors involved in species- specificity and control of mouse ribosomal gene transcription." In Molecular Mechanisms of Cellular Growth. Springer US, 1991. http://dx.doi.org/10.1007/978-1-4615-3886-8_17.
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Boado, Ruben J. "Post-transcription modulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived factors." In Advances in Dementia Research. Springer Vienna, 2000. http://dx.doi.org/10.1007/978-3-7091-6781-6_27.
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Kaitsuka, Taku, and Kazuhito Tomizawa. "Generation of Functional Insulin-Producing Cells from Mouse Embryonic Stem Cells Through Protein of Transcription Factors." In Methods in Molecular Biology. Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0943-9_7.
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Ito, Yoshihisa, Kumiko Ishige, Masahiro Aizawa, and Hideomi Fukuda. "GABAB Antagonists Block γ-Butyrolactone-Induced Absence Seizures and Coordinated Induction of Transcription Factors in Mouse Brain." In GABA: Receptors, Transporters and Metabolism. Birkhäuser Basel, 1996. http://dx.doi.org/10.1007/978-3-0348-8990-2_35.
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Gagliardi, Francesco, and Claudia Angelini. "Discovering Typical Transcription-Factors Patterns in Gene Expression Levels of Mouse Embryonic Stem Cells by Instance-Based Classifiers." In New Trends in Image Analysis and Processing – ICIAP 2013. Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-41190-8_41.
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Qiu, Boning, Ruben J. de Vries, and Massimiliano Caiazzo. "Direct Cell Reprogramming of Mouse Fibroblasts into Functional Astrocytes Using Lentiviral Overexpression of the Transcription Factors NFIA, NFIB, and SOX9." In Methods in Molecular Biology. Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1601-7_3.
Full textConference papers on the topic "Mouse Derived Transcription Factors"
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Liu Yang, Jin Bo, Guo Bin, et al. "Expressions of transcription factors Ets1 and Ets2 in mouse testis tissue." In 2011 International Conference on Remote Sensing, Environment and Transportation Engineering (RSETE). IEEE, 2011. http://dx.doi.org/10.1109/rsete.2011.5965935.
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Miyake*, Shinji, Hiroyuki Kuraoka**, and Chikamune Wada**. "Heart Rate Variability as a Mental Workload Index." In Applied Human Factors and Ergonomics Conference. AHFE International, 2021. http://dx.doi.org/10.54941/ahfe100642.
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In this study, we investigated relationship between task characteristics such as sensory intake and cardiovascular responses. Nineteen male participants were asked to perform a mental arithmetic task (MA) and a computerized mirror tracing (MT) task for five minutes each. In the MA task, participants were instructed to respond within five seconds by pressing the left or right mouse button. Therefore, this task includes a high time pressure (temporal restriction). In the MT task, participants were required to trace a zigzag pathway displayed on a PC screen by using a mouse. The horizontal and vertical control elements of the mouse were exchanged with each other. This task contains a sensory intake characteristic which induces parasympathetic dominance resulting in bradycardia. ECG and arterial blood pressure were continuously recorded during the two task blocks and before (PRE) and after (POST) resting periods of five minutes each. Heart rate variability indexes such as low frequency (LF) component, high frequency (HF) component and LF/HF ratio were derived. In the results, heart rate (HR) was considerably larger in the MA compared to PRE. On the contrary, the HR change was small in the MT, suggesting that the physiological response in MT is a pattern 2 type which is typically induced by a sensory intake task, although no significant difference was found between the two tasks. Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) were higher in the MT than MA, but there was no significant difference between them. Both SBP and DBP were significantly higher in the task periods than resting periods. Significant differences were found only between PRE and MT, and PRE and POST in LF/HF which showed the highest value in POST, suggesting that the LF/HF ratio is not a reliable mental workload index.
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Jamal, Mohammad S., Bilal B. Hafeez, and Ajit K. Verma. "Abstract 4204: Chronic ultraviolet radiation exposure of mouse skin activates GATA and PAX families of transcription factors, which regulate expression of cell survival genes." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-4204.
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Xie, Jianping, Paul Rivas, Anuradha Soundararajan, et al. "Abstract 851: Interactions among transcription factors as a potential mechanism for inhibiting castrate-resistant prostate cancer (CRPCa) in transgenic adenocarcinoma of mouse prostate (TRAMP) through regulation of FLIP." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-851.
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Balaji, Swathi, Sachin S. Vaikunth, Jignesh K. Parvadia, Timothy M. Crombleholme, and Daria A. Narmoneva. "In Situ Tissue Engineering Using Angiogenic Nanoscaffold Enhances Diabetic Wound Healing in db/db Mouse Model." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-192198.
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Tissue engineering offers an attractive alternative for treatment of chronic nonhealing diabetic ulcers, which account for more than 27% of the $10.9 billion total diabetic health care costs in the US annually [1]. The harsh environment of a diabetic ulcer is characterized by reduced expression of angiogenic factors, insufficient vascularization, excess protease activity, matrix degradation and hyperglycemia-induced cell apoptosis [2]. A major factor contributing to insufficient neovascularization in diabetic nonhealing wounds may be deficiency in the recruitment of endothelial cells (ECs) and endothelial precursor cells (EPCs) to the wound site [3]. Recent studies focusing on altering the wound’s cellular and molecular environment using bone-marrow-derived stem cells, growth factors (delivered either directly or using gene or cell therapy), bioengineered skin constructs, and biological matrices, such as collagen and hyaluronic acid gels had promising wound healing outcomes [4]. These studies suggest that strategies aimed at modifying the extracellular environment of the diabetic wound to enhance cell survival and angiogenesis are promising for development of new therapies for diabetic wound healing.
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Park, Heesook, Do Young Lim, Minhee Kim, and Jung Han Yoon Park. "Abstract 1823: Chronic consumption of a high-fat diet stimulates tumor growth and metastasis via the activation of key transcription factors in a CT26 mouse colon cancer allograft model." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-1823.
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He, Weihong, Hengshu Chen, Kexin Chen, Tiantian Li, Simiao Wu, and Si Wang. "Pharmacological Inhibition of RUNX1 Suppresses Cardiac Cathepsin Expression and Preserves Cardiac Function Following Myocardial Infarction in Rats." In International Medicine and Health Sciences Congress. ECER, 2024. https://doi.org/10.53375/imhsc.2024.52.
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Cardiac cell death following myocardial infarction (MI) leads to irreversible loss of myocardium which in turn leads to adverse structural and functional changes of the heart, referred to as cardiac remodelling. Progression of adverse remodelling causes heart failure which is linked to increased deaths or hospitalizations. Runt-related transcription factor-1 (RUNX1) is a member of the core-binding factor family of transcription factors which regulate gene expression. Recent evidence showed that RUNX1 expression is increased following MI and negatively correlates with cardiac function. Dr He’s previous study performed with a cardiomyocyte-specific Runx1-deficient mouse revealed that reducing RUNX1 function preserves myocardial contractility and prevents adverse cardiac remodeling. Cathepsin is a family of lysosomal proteases and is involved in multiple cell death pathways. Our recent study showed that inhibition of RUNX1 reduced infarct size after acute MI, paralleled with repressed cardiac cathepsin levels. The present work sought to investigate whether the inhibition of RUNX1 preserves cardiac function post-MI. MI was surgically induced by performing coronary artery ligation and echocardiography was used to assess cardiac function. Here, we report that cardiac systolic function, as indicated by fractional shortening, decreased in control rats. In contrast, rats treated with RUNX1 inhibitor Ro5-3335 demonstrated a markedly preserved fractional shortening that was 128% of the control animal at 1-week post-MI (39.1±1.4% versus 30.6±2.9%; P<0.05). This beneficial effect is in line with our previous work and might be due to repressed cathepsin expression as revealed by our recent proteomic study. Taken together, our data demonstrate that pharmacological inhibition of RUNX1 not only reduces infarct size but also preserves cardiac function following MI, thereby suggesting the translational potential of RUNX1 as a new therapeutic target for cardiac protection against MI.
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Shikata, Tetsuo, Toshihiko Shiraishi, Kumiko Tanaka, Shin Morishita, and Ryohei Takeuchi. "Effects of Acceleration Amplitude and Frequency of Mechanical Vibration on Osteoblast-Like Cells." In ASME 2007 International Mechanical Engineering Congress and Exposition. ASMEDC, 2007. http://dx.doi.org/10.1115/imece2007-41797.
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Bone formation is subject in vivo to mechanical stimulation. Although many researches for bone cells of osteoblastic lineage sensing and responding to mechanical stimulation have been reported mainly in the biochemical field, effects of mechanical stimulation on bone cells are not well understood. In this study, in order to clarify effects of acceleration amplitude and frequency of mechanical stimulation on MC3T3-E1, which is an osteoblast-like cell line derived from mouse calvaria, in the sense of mechanical vibrations, their cell proliferation, cell morphology, bone matrix generation and gene expression of alkaline phosphatase (ALP) were investigated when sinusoidal inertia force was applied to the cells. After the cells were cultured in culture plates in a CO2 incubator for one day and adhered on the cultured plane, vibrating groups of the culture plates were set on an aluminum plate attached to a exciter and cultured under sinusoidal excitation in another incubator separated from non-vibrating groups of the culture plates. Acceleration amplitude and frequency were set to several kinds of conditions. The time evolution of cell density was obtained by counting the number of cells with a hemocytometer. The cell morphology was observed with a phase contrast microscope. Calcium salts generated by the cells were observed by being stained with alizarin red S solution and their images were captured with a CCD camera. The vibrating groups for the cell proliferation and the calcium salts staining were sinusoidally excited for 24 hours a day during 28-day cultivation. Gene expression of ALP was measured by a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) method. After the vibrating groups for the PCR were excited for 7 days, the total RNAs were extracted. After reverse transcription, real-time RT-PCR was performed. Gene expression for ALP and a housekeeping gene were determined simultaneously for each sample. ALP gene level in each sample was normalized to the measured housekeeping gene level. The results to be obtained are as follows. In the range from 12.5 to 200 Hz, saturation cell density for the cell proliferation shows tendency of increase as frequency decreases and ALP gene expression shows a peak to frequency at 50 Hz. Among 0, 0.25 and 0.5 G, saturation cell density and ALP gene expression show tendency of increase as acceleration amplitude increases.
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Bernhagen, Max, and Angelika C Bullinger. "Towards Reliable Tactile Mid-Air Interfaces: Analysis of Influencing Factors of the Perception of Tactile Mid-Air Feedback." In 8th International Conference on Human Interaction and Emerging Technologies. AHFE International, 2022. http://dx.doi.org/10.54941/ahfe1002760.
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Human-machine interfaces require an efficient and reliable interaction under various con-ditions. Especially under conditions with high cognitive workload which require rapid situa-tion assessment, interfaces should reliably support the human perception. Here, research addresses gesture-based interfaces as a possible interface to enable intuitive interactions based on ingrained daily routines. Using spatial commands executed by the bare hand, one can recreate real world interactions like pushing a knob, turning a controller, or using a ges-ture as an input command. In comparison to real input devices gesture-based interfaces lack haptic feedback for the user. Tactile feedback is important as it indicates for example interaction borders (e. g. edge of the mouse pad) or provides feedback of a successful in-teraction (e. g. sensation of the pushed button). This helps to increase the usability of mid-air gestural systems. For the realisation of mid-air tactile feedback two technologies can be considered. Vortex-generators and ultrasound-based feedback utilise the bare hand and need no device attached to the hand. However, they provide weak feedback which can be influenced by airflow, hand posture, clothing, workload or other factors. To achieve the aforementioned benefits, users have to reliably perceive the tactile feedback – and to do so, perception of tactile mid-air feedback needs to be researched in more detail.We present a method for the analysis of influencing factors on the perception. A driving simulator was the basis for a standardised apparatus in which tactile feedback was pre-sented via a vortex-generator. For each influencing factor, participants were asked to do a driving task (Lane Change Task - LCT) and detect tactile stimuli in parallel. By the help of the method of constant stimuli, a psychometric function for each influencing factor was derived. On this function detection, thresholds of 50%, 90%, 95% and 99% were chosen to represent the most important values in terms of human-machine interaction. In compari-son to widely used methods like staircase procedures, this approach promises to give a better insight into the effects of the influencing factors as the whole psychometric func-tion can be analysed instead of one distinct value.Two experiments (N= 80; 31) were conducted to apply the approach and analyse the influ-ence of workload by a variation of speed and secondary task type. Also, one experiment (N= 16) investigated the influence of hand temperature on the perception of the feedback. Results show that increased speed and the addition of a secondary tasks significantly in-crease the perceived workload. Regarding the perception of tactile stimuli, slight differ-ences for different workload conditions and a cut-off for high workload conditions were found. Furthermore, the effect of temperature on the perception on tactile feedback could be shown. Based on the studies, advantages and disadvantages of the proposed approach are dis-cussed. Also, the impact of workload and temperature in terms of design recommenda-tions for human-machine interaction are examined. The presented approach suggests a promising method to investigate the impact of influencing factors on specific design ele-ments for human-computer interaction. Further studies should investigate the eligibility for other modalities and applications.
Reports on the topic "Mouse Derived Transcription Factors"
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Splitter, Gary A., Menachem Banai, and Jerome S. Harms. Brucella second messenger coordinates stages of infection. United States Department of Agriculture, 2011. http://dx.doi.org/10.32747/2011.7699864.bard.
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Aim 1: To determine levels of this second messenger in: a) B. melitensiscyclic-dimericguanosinemonophosphate-regulating mutants (BMEI1448, BMEI1453, and BMEI1520), and b) B. melitensis16M (wild type) and mutant infections of macrophages and immune competent mice. (US lab primary) Aim 2: To determine proteomic differences between Brucelladeletion mutants BMEI1453 (high cyclic-dimericguanosinemonophosphate, chronic persistent state) and BMEI1520 (low cyclicdimericguanosinemonophosphate, acute virulent state) compared to wild type B. melitensisto identify the role of this second messenger in establishing the two polar states of brucellosis. (US lab primary with synergistic assistance from the Israel lab Aim 3: Determine the level of Brucellacyclic-dimericguanosinemonophosphate and transcriptional expression from naturally infected placenta. (Israel lab primary with synergistic assistance from the US lab). B. Background Brucellaspecies are Gram-negative, facultative intracellular bacterial pathogens that cause brucellosis, the most prevalent zoonosis worldwide. Brucellosis is characterized by increased abortion, weak offspring, and decreased milk production in animals. Humans are infected with Brucellaby consuming contaminated milk products or via inhalation of aerosolized bacteria from occupational hazards. Chronic human infections can result in complications such as liver damage, orchitis, endocarditis, and arthritis. Brucellaspp. have the ability to infect both professional and non-professional phagocytes. Because of this, Brucellaencounter varied environments both throughout the body and within a cell and must adapt accordingly. To date, few virulence factors have been identified in B. melitensisand even less is known about how these virulence factors are regulated. Subsequently, little is known about how Brucellaadapt to its rapidly changing environments, and how it alternates between acute and chronic virulence. Our studies suggest that decreased concentrations of cyclic dimericguanosinemonophosphate (c-di-GMP) lead to an acute virulent state and increased concentrations of c-di-GMP lead to persistent, chronic state of B. melitensisin a mouse model of infection. We hypothesize that B. melitensisuses c-di-GMP to transition from the chronic state of an infected host to the acute, virulent stage of infection in the placenta where the bacteria prepare to infect a new host. Studies on environmental pathogens such as Vibrio choleraeand Pseudomonas aeruginosasupport a mechanism where changes in c-di-GMP levels cause the bacterium to alternate between virulent and chronic states. Little work exists on understanding the role of c-di-GMP in dangerous intracellular pathogens, like Brucellathat is a frequent pathogen in Israeli domestic animals and U.S. elk and bison. Brucellamust carefully regulate virulence factors during infection of a host to ensure proper expression at appropriate times in response to host cues. Recently, the novel secondary signaling molecule c-di-GMP has been identified as a major component of bacterial regulation and we have identified c-di-GMP as an important signaling factor in B. melitensishost adaptation. C. Major conclusions, solutions, achievements 1. The B. melitensis1453 deletion mutant has increased c-di-GMP, while the 1520 deletion mutant has decreased c-di-GMP. 2. Both mutants grow similarly in in vitro cultures; however, the 1453 mutant has a microcolony phenotype both in vitro and in vivo 3. The 1453 mutant has increased crystal violet staining suggesting biofilm formation. 4. Scanning electron microscopy revealed an abnormal coccus appearance with in increased cell area. 5. Proteomic analysis revealed the 1453 mutant possessed increased production of proteins involved in cell wall processes, cell division, and the Type IV secretion system, and a decrease in proteins involved in amino acid transport/metabolism, carbohydrate metabolism, fatty acid production, and iron acquisition suggesting less preparedness for intracellular survival. 6. RNAseq analysis of bone marrow derived macrophages infected with the mutants revealed the host immune response is greatly reduced with the 1453 mutant infection. These findings support that microlocalization of proteins involved in c-di-GMP homeostasis serve a second messenger to B. melitensisregulating functions of the bacteria during infection of the host.
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Yu, Mei, Pengyu Wang, Binbin Li, et al. NRSF Negatively Regulates Microglial Pro-Inflammatory Activation. Progress in Neurobiology, 2024. http://dx.doi.org/10.60124/j.pneuro.2024.20.02.
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Microglial activation contributes to neurological disorders like Parkinson’s disease (PD), and modulating this activation is a potential therapeutic approach. The neuron-restrictive silencer factor (NRSF) functions as a negative regulator of gene transcription through epigenetic modifications. While previous research has primarily examined the role of NRSF in neuronal differentiation and injury, emerging evidence indicates that NRSF also plays a significant role in maintaining the phenotype of glial cells. In this study, we explored the role and underlying mechanisms of NRSF in lipopolysaccharide (LPS)-induced pro-inflammatory or interleukin-4 (IL4)-induced anti-inflammatory phenotype of microglial activation. Following LPS stimulation, the nuclear localization of NRSF increased in BV2 microglial cells, primary mouse microglia, and microglia within the substantia nigra of PD mice. Knockdown of NRSF enhanced the expression of inflammation-related factors induced by LPS via the mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) and nuclear factor-κB (NF-κB) p65 signalling pathways in BV2 cells. Moreover, the culture medium from LPS-treated NRSF knockdown BV2 cells exerted greater toxic effects on human neuroblastoma SH-SY5Y cells compared to the control. However, NRSF knockdown exerted inconsistent effects on the expression of anti-inflammatory-related genes in IL4-treated BV2 cells. Our findings suggest that NRSF knockdown promotes microglial pro-inflammatory activation.
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Elroy-Stein, Orna, and Dmitry Belostotsky. Mechanism of Internal Initiation of Translation in Plants. United States Department of Agriculture, 2010. http://dx.doi.org/10.32747/2010.7696518.bard.
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Original objectives Elucidation of PABP's role in crTMV148 IRES function in-vitro using wheat germ extract and krebs-2 cells extract. Fully achieved. Elucidation of PABP's role in crTMV148 IRES function in-vivo in Arabidopsis. Characterization of the physical interactions of PABP and other potential ITAFs with crTMV148 IRES. Partly achieved. To conduct search for additional ITAFs using different approaches and evaluate the candidates. Partly achieved. Background of the topic The power of internal translation via the activity of internal ribosomal entry site (IRES) elements allow coordinated synthesis of multiple gene products from a single transcription unit, and thereby enables to bypass the need for sequential transformation with multiple independent transgenes. The key goal of this project was to identify and analyze the IRES-trans-acting factors (ITAFs) that mediate the activity of a crucifer-infecting tobamovirus (crTMV148) IRES. The remarkable conservation of the IRES activity across the phylogenetic spectrum (yeast, plants and animals) strongly suggests that key ITAFs that mediate its activity are themselves highly conserved. Thus, crTMV148 IRES offers opportunity for elucidation of the fundamental mechanisms underlying internal translation in higher plants in order to enable its rational manipulation for the purpose of agricultural biotechnology. Major conclusions and achievements. - CrTMV IRES requires PABP for maximal activity. This conclusion was achieved by PABP depletion and reconstitution of wheat germ- and Krebs2-derived in-vitro translation assays using Arabidopsis-derived PABP2, 3, 5, 8 and yeast Pab1p. - Mutations in the internal polypurine tract of the IRES decrease the high-affinity binding of all phylogenetically divergent PABPs derived from Arabidopsis and yeast in electro mobility gel shift assays. - Mutations in the internal polypurine tract decrease IRES activity in-vivo. - The 3'-poly(A) tail enhances crTMV148 IRES activity more efficiently in the absence of 5'-methylated cap. - In-vivo assembled RNPs containing proteins specifically associated with the IRES were purified from HEK293 cells using the RNA Affinity in Tandem (RAT) approach followed by their identification by mass spectroscopy. - This study yielded a list of potential protein candidates that may serve as ITAFs of crTMV148 IRES activity, among them are a/b tubulin, a/g actin, GAPDH, enolase 1, ribonuclease/angiogenin inhibitor 1, 26S proteasome subunit p45, rpSA, eEF1Bδ, and proteasome b5 subunit. Implications, both scientific and agriculture. The fact that the 3'-poly(A) tail enhances crTMV148 IRES activity more efficiently in the absence of 5'-methylated cap suggests a potential joint interaction between PABP, the IRES sequence and the 3'-poly(A). This has an important scientific implication related to IRES function in general.
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Firon, Nurit, Prem Chourey, Etan Pressman, Allen Hartwell, and Kenneth J. Boote. Molecular Identification and Characterization of Heat-Stress-Responsive Microgametogenesis Genes in Tomato and Sorghum - A Feasibility Study. United States Department of Agriculture, 2007. http://dx.doi.org/10.32747/2007.7591741.bard.
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Exposure to higher than optimal temperatures - heat-stress (HS) - is becoming increasingly common to all crop plants worldwide. Heat stress coinciding with microgametogenesis, especially during the post-meiotic phase that is marked by starch biosynthesis, is often associated with starch-deficient pollen and male sterility and ultimately, greatly reduced crop yields. The molecular basis for the high sensitivity of developing pollen grains, on one hand, and factors involved in pollen heat-tolerance, on the other, is poorly understood. The long-term goal of this project is to provide a better understanding of the genes that control pollen quality under heat-stress conditions. The specific objectives of this project were: (1) Determination of the threshold heat stress temperature(s) that affects tomato and sorghum pollen quality whether: a) Chronic mild heat stress conditions (CMHS), or b) Acute heat stress (AHS). (2) Isolation of heat-responsive, microgametogenesis-specific sequences. During our one-year feasibility project, we have accomplished the proposed objectives as follows: Objectrive 1: We have determined the threshold HS conditions in tomato and sorghum. This was essential for achieving the 2nd objective, since our accumulated experience (both Israeli and US labs) indicate that when temperature is raised too high above "threshold HS levels" it may cause massive death of the developing pollen grains. Above-threshold conditions have additional major disadvantages including the "noise" caused by induced expression of genes involved in cell death and masking of the differences between heatsensitive and heat-tolerant pollen grains. Two different types of HS conditions were determined: a) Season-long CMHS conditions: 32/26°C day/night temperatures confirmed in tomato and 36/26°C day maximum/night minimum temperatures in sorghum. b) Short-term AHS: In tomato, 2 hour exposure to 42-45°C (at 7 to 3 days before anthesis) followed by transfer to 28/22±2oC day/night temperatures until flower opening and pollen maturation, caused 50% reduced germinating pollen in the heat-sensitive 3017 cv.. In sorghum, 36/26°C day/night temperatures 10 to 5 days prior to panicle emergence, occurring at 35 days after sowing (DAS) in cv. DeKalb28E, produced starch-deficient and sterile pollen. Objective 2: We have established protocols for the high throughput transcriptomic approach, cDNA-AFLP, for identifying and isolating genes exhibiting differential expression in developing microspores exposed to either ambient or HS conditions and created a databank of HS-responsivemicrogametogenesis-expressed genes. A subset of differentially displayed Transcript-Derived Fragments (TDFs) that were cloned and sequenced (35 & 23 TDFs in tomato and sorghum, respectively) show close sequence similarities with metabolic genes, genes involved in regulation of carbohydrate metabolism, genes implicated in thermotolerance (heat shock proteins), genes involved in long chain fatty acids elongation, genes involved in proteolysis, in oxidation-reduction, vesicle-mediated transport, cell division and transcription factors. T-DNA-tagged Arabidopsis mutants for part of these genes were obtained to be used for their functional analysis. These studies are planned for a continuation project. Following functional analyses of these genes under HS – a valuable resource of genes, engaged in the HS-response of developing pollen grains, that could be modulated for the improvement of pollen quality under HS in both dicots and monocots and/or used to look for natural variability of such genes for selecting heat-tolerant germplasm - is expected.
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Fridman, Eyal, and Eran Pichersky. Tomato Natural Insecticides: Elucidation of the Complex Pathway of Methylketone Biosynthesis. United States Department of Agriculture, 2009. http://dx.doi.org/10.32747/2009.7696543.bard.
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Plant species synthesize a multitude of specialized compounds 10 help ward off pests. and these in turn may well serve as an alternative to synthetic pesticides to reduce environmental damage and health risks to humans. The general goal of this research was to perform a genetic and biochemical dissection of the natural-insecticides methylketone pathway that is specific to the glandular trichomes of the wild species of tomato, Solanumhabrochaites f. glabratum (accession PI126449). Previous study conducted by us have demonstrated that these compounds are synthesized de novo as a derivate pathway of the fatty acid biosynthesis, and that a key enzyme. designated MethylketoneSynthase 1 (MKS 1). catalyzes conversion of the intermediate B-ketoacyl- ACPs to the corresponding Cn-1 methylketones. The approach taken in this proposed project was to use an interspecific F2 population. derived from the cross between the cultivated lV182 and the wild species PIl26449. for three objectives: (i) Analyze the association between allelic status of candidate genes from the fatty acid biosynthesis pathway with the methylketone content in the leaves (ii) Perform bulk segregant analysis of genetic markers along the tomato genome for identifying genomic regions that harbor QTLs for 2TD content (iii) Apply differential gene expression analysis using the isolated glands of bulk segregant for identifying new genes that are involved in the pathway. The genetic mapping in the interspecific F2 population included app. 60 genetic markers, including the candidate genes from the FAS pathway and SSR markers spread evenly across the genome. This initial; screening identified 5 loci associated with MK content including the candidate genes MKS1, ACC and MaCoA:ACP trans. Interesting observation in this genetic analysis was the connection between shape and content of the glands, i.e. the globularity of the four cells, typical to the wild species. was associated with increased MK in the segregating population. In the next step of the research transcriptomic analysis of trichomes from high- and 10w-MK plants was conducted. This analysis identified a new gene, Methy1ketone synthase 2 (MKS2), whose protein product share sequence similarity to the thioesterase super family of hot-dog enzymes. Genetic analysis in the segregating population confirmed its association with MK content, as well as its overexpression in E. coli that led to formation of MK in the media. There are several conclusions drawn from this research project: (i) the genetic control of MK accumulation in the trichomes is composed of biochemical components in the FAS pathway and its vicinity (MKS 1 and MKS2). as well as genetic factors that mediate the morphology of these specialized cells. (ii) the biochemical pathway is now realized different from what was hypothesized before with MKS2 working upstream to I\1KS 1 and serves as the interface between primary (fatty acids) and secondary (MK) metabolism. We are currently testing the possible physical interactions between these two proteins in vitro after the genetic analysis showed clear epistatic interactions. (iii) the regulation of the pathway that lead to specialized metabolism in the wild species is largely mediated by transcription and one of the achievements of this project is that we were able to isolate and verify the specificity of the MKS1 promoter to the trichomes which allows manipulation of the pathways in these cells (currently in progress). The scientific implications of this research project is the advancement in our knowledge of hitherto unknown biochemical pathway in plants and new leads for studying a new family in plants (hot dog thioesterase). The agricultural and biotechnological implication are : (i) generation of new genetic markers that could assist in importing this pathway to cultivated tomato hence enhancing its natural resistance to insecticides, (ii) the discovery of MKS2 adds a new gene for genetic engineering of plants for making new fatty acid derived compounds. This could be assisted with the use of the isolated and verified MKS1 promoter. The results of this research were summarized to a manuscript that was published in Plant Physiology (cover paper). to a chapter in a proceeding book. and one patent was submitted in the US.