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In somatic cells, the mitotic spindle apparatus is centrosomal and several isoforms of Protein Kinase C (PKC) have been associated with the mitotic spindle, but their role in stabilizing the mitotic spindle is unclear. Other protein kinases such as, Glycogen Synthase Kinase 3â (GSK3â) also have been shown to be

In somatic cells, the mitotic spindle apparatus is centrosomal and several isoforms of Protein Kinase C (PKC) have been associated with the mitotic spindle, but their role in stabilizing the mitotic spindle is unclear. Other protein kinases such as, Glycogen Synthase Kinase 3â (GSK3â) also have been shown to be associated with the mitotic spindle. In the study in chapter 2, we show the enrichment of active (phosphorylated) PKCæ at the centrosomal region of the spindle apparatus in metaphase stage of 3T3 cells. In order to understand whether the two kinases, PKC and GSK3â are associated with the mitotic spindle, first, the co-localization and close molecular proximity of PKC isoforms with GSK3â was studied in metaphase cells. Second, the involvement of inactive GSK3â in maintaining an intact mitotic spindle was shown. Third, this study showed that addition of a phospho-PKCæ specific inhibitor to cells can disrupt the mitotic spindle microtubules. The mitotic spindle at metaphase in mouse fibroblasts appears to be maintained by PKCæ acting through GSK3â. The MAPK pathway has been implicated in various functions related to cell cycle regulation. MAPKK (MEK) is part of this pathway and the extracellular regulated kinase (ERK) is its known downstream target. GSK3â and PKCæ also have been implicated in cell cycle regulation. In the study in chapter 3, we tested the effects of inhibiting MEK on the activities of ERK, GSK3â, PKCæ, and á-tubulin. Results from this study indicate that inhibition of MEK did not inhibit GSK3â and PKCæ enrichment at the centrosomes. However, the mitotic spindle showed a reduction in the pixel intensity of microtubules and also a reduction in the number of cells in each of the M-phase stages. A peptide activation inhibitor of ERK was also used. Our results indicated a decrease in mitotic spindle microtubules and an absence of cells in most of the M-phase stages. GSK3â and PKCæ enrichment were however not inhibited at the centrosomes. Taken together, the kinases GSK3â and PKCæ may not function as a part of the MAPK pathway to regulate the mitotic spindle.
ContributorsChakravadhanula, Madhavi (Author) / Capco, David G. (Thesis advisor) / Chandler, Douglas (Committee member) / Clark-Curtiss, Josephine (Committee member) / Newfeld, Stuart (Committee member) / Arizona State University (Publisher)
Created2012
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In the early twentieth century, Paul Kammerer conducted a series of experiments to demonstrate that organisms could transmit characteristics acquired in their lifetimes to their offspring. In his 1809 publication, zoologist Jean-Baptiste Lamarck had hypothesized that living beings can inherit features their parents or ancestors acquired throughout life. By breeding

In the early twentieth century, Paul Kammerer conducted a series of experiments to demonstrate that organisms could transmit characteristics acquired in their lifetimes to their offspring. In his 1809 publication, zoologist Jean-Baptiste Lamarck had hypothesized that living beings can inherit features their parents or ancestors acquired throughout life. By breeding salamanders, as well as frogs and other organisms, Kammerer tested Lamarck's hypothesis in an attempt to provide evidence for Lamarck's theory of the inheritance of acquired characteristics. In particular, Kammerer argued that the inheritance of acquired characteristics caused species to evolve, and he claimed that his results provided an explanation for evolutionary processes through developmental phenomena.

Created2014-12-30
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Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called

Aristotle studied developing organisms, among other things, in ancient Greece, and his writings shaped Western philosophy and natural science for greater than two thousand years. He spent much of his life in Greece and studied with Plato at Plato's Academy in Athens, where he later established his own school called the Lyceum. Aristotle wrote greater than 150 treatises on subjects ranging from aesthetics, politics, ethics, and natural philosophy, which include physics and biology. Less than fifty of Aristotle's treatises persisted into the twenty-first century. In natural philosophy, later called natural science, Aristotle established methods for investigation and reasoning and provided a theory on how embryos generate and develop. He originated the theory that an organism develops gradually from undifferentiated material, later called epigenesis.

Created2016-07-07
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Paul Kammerer conducted experiments on amphibians and marine animals at the Vivarium, a research institute in Vienna, Austria, in the early twentieth century. Kammerer bred organisms in captivity, and he induced them to develop particular adaptations, which Kammerer claimed the organismss offspring would inherit. Kammerer argued that his results demonstrated

Paul Kammerer conducted experiments on amphibians and marine animals at the Vivarium, a research institute in Vienna, Austria, in the early twentieth century. Kammerer bred organisms in captivity, and he induced them to develop particular adaptations, which Kammerer claimed the organismss offspring would inherit. Kammerer argued that his results demonstrated the inheritance of acquired characteristics, or Lamarckian inheritance. The Lamarckian theory of inheritance posits that individuals transmit acquired traits to their offspring. Kammerer worked during a period in which scientists debated how variation between organisms and within species was caused, and how organisms could inherit that variation from their parents. Kammerer contended that the inheritance of acquired characteristics occurs during embryological development, but several scientists argued that he provided poor evidence for his claims.

Created2014-11-25
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The Cell-Theory was written by Thomas Henry Huxley in Britain and published in 1853 by The British and Foreign Medico-Chirurgical Review. The twenty-two page article reviews twelve works on cell theory, including those in Germany by Caspar Friedrich Wolff in the eighteenth century and by Karl Ernst von Baer in

The Cell-Theory was written by Thomas Henry Huxley in Britain and published in 1853 by The British and Foreign Medico-Chirurgical Review. The twenty-two page article reviews twelve works on cell theory, including those in Germany by Caspar Friedrich Wolff in the eighteenth century and by Karl Ernst von Baer in the nineteenth century. Huxley spends much of The Cell-Theory on a cell theory proposed in the late 1830s by Matthias Schleiden and Theodor Schwann in Germany. Schleiden and Schwann maintained that the cell was the most fundamental unit of life and that the nucleus was the most significant cellular component. Huxley, instead, promoted an epigenetic theory of the cell, for which properties of life emerge from the outer cytoplasm, cell membrane, and wall (the periplast), as opposed to the inner contents of the cell, including the nucleus (the endoplast). Huxley's arguments in The Cell-Theory influenced future scientists about the role of epigenetic processes in embryology and development.

Created2013-12-12
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In "Behavioral Thermoregulation by Turtle Embryos," published in Proceedings of the National Academy of Sciences in April, 2011, Wei-Guo Du, Bo Zhao, Ye Chen, and Richard Shine report that turtle embryos can move towards warmer temperatures within the egg when presented with a small, 0.8 degrees Celsius gradient. This behavioral

In "Behavioral Thermoregulation by Turtle Embryos," published in Proceedings of the National Academy of Sciences in April, 2011, Wei-Guo Du, Bo Zhao, Ye Chen, and Richard Shine report that turtle embryos can move towards warmer temperatures within the egg when presented with a small, 0.8 degrees Celsius gradient. This behavioral thermoregulation may benefit the embryo's fitness by accelerating the rate of development enough to decrease the incubation period by up to four and a half days. Embryos are generally thought to have little control over their surroundings. This study revealed that embryos may be able to control their developmental environment by modifying their behavior.

Created2012-09-20
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In 2002 Eric Davidson and his research team published 'A Genomic Regulatory Network for Development' in Science. The authors present the first experimental verification and systemic description of a gene regulatory network. This publication represents the culmination of greater than thirty years of work on gene regulation that began in

In 2002 Eric Davidson and his research team published 'A Genomic Regulatory Network for Development' in Science. The authors present the first experimental verification and systemic description of a gene regulatory network. This publication represents the culmination of greater than thirty years of work on gene regulation that began in 1969 with 'A Gene Regulatory Network for Development: A Theory' by Roy Britten and Davidson. The modeling of a large number of interactions in a gene network had not been achieved before. Furthermore, this model revealed behaviors of the gene networks that could only be observed at the levels of biological organization above that of the gene.

Created2013-10-11
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Paul M. Brakefield and his research team in Leiden, the Netherlands, examined the development, plasticity, and evolution of butterfly eyespot patterns, and published their findings in Nature in 1996. Eyespots are eye-shaped color patterns that appear on the wings of some butterflies and birds as well as on the skin

Paul M. Brakefield and his research team in Leiden, the Netherlands, examined the development, plasticity, and evolution of butterfly eyespot patterns, and published their findings in Nature in 1996. Eyespots are eye-shaped color patterns that appear on the wings of some butterflies and birds as well as on the skin of some fish and reptiles. In butterflies, such as the peacock butterfly Aglais, the eyespots resemble the eyes of birds and help butterflies deter potential predators. Brakefield's research team described the stages through which eyespots develop, identified the genes and environmental signals that affect eye-spot appearance in some species, and demonstrated that small genetic variations can change butterfly eyespot color and shape. The research focused on a few butterfly species, but it contributed to more general claims of how the environment may affect the development of coloration and how specific color patterns may have evolved.

Created2013-09-10
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In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene

In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.

Created2013-09-10
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Systems biology studies complex biological systems. It is an interdisciplinary field, with biologists working with non-biologists such as computer scientists, engineers, chemists, and mathematicians to address research problems applying systems’ perspectives. How these different researchers and their disciplines differently contributed to the advancement of this field over time is a

Systems biology studies complex biological systems. It is an interdisciplinary field, with biologists working with non-biologists such as computer scientists, engineers, chemists, and mathematicians to address research problems applying systems’ perspectives. How these different researchers and their disciplines differently contributed to the advancement of this field over time is a question worth examining. Did systems biology become a systems-oriented science or a biology-oriented science from 1992 to 2013?

This project utilized computational tools to analyze large data sets and interpreted the results from historical and philosophical perspectives. Tools deployed were derived from scientometrics, corpus linguistics, text-based analysis, network analysis, and GIS analysis to analyze more than 9000 articles (metadata and text) on systems biology. The application of these tools to a HPS project represents a novel approach.

The dissertation shows that systems biology has transitioned from a more mathematical, computational, and engineering-oriented discipline focusing on modeling to a more biology-oriented discipline that uses modeling as a means to address real biological problems. Also, the results show that bioengineering and medical research has increased within systems biology. This is reflected in the increase of the centrality of biology-related concepts such as cancer, over time. The dissertation also compares the development of systems biology in China with some other parts of the world, and reveals regional differences, such as a unique trajectory of systems biology in China related to a focus on traditional Chinese medicine.

This dissertation adds to the historiography of modern biology where few studies have focused on systems biology compared with the history of molecular biology and evolutionary biology.
ContributorsZou, Yawen (Author) / Laubichler, Manfred (Thesis advisor) / Maienschein, Jane (Thesis advisor) / Creath, Richard (Committee member) / Ellison, Karin (Committee member) / Newfeld, Stuart (Committee member) / Arizona State University (Publisher)
Created2016