Matching Items (62)
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Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments

Once perceived as an unimportant occurrence in living organisms, cell degeneration was reconfigured as an important biological phenomenon in development, aging, health, and diseases in the twentieth century. This dissertation tells a twentieth-century history of scientific investigations on cell degeneration, including cell death and aging. By describing four central developments in cell degeneration research with the four major chapters, I trace the emergence of the degenerating cell as a scientific object, describe the generations of a variety of concepts, interpretations and usages associated with cell death and aging, and analyze the transforming influences of the rising cell degeneration research. Particularly, the four chapters show how the changing scientific practices about cellular life in embryology, cell culture, aging research, and molecular biology of Caenorhabditis elegans shaped the interpretations about cell degeneration in the twentieth-century as life-shaping, limit-setting, complex, yet regulated. These events created and consolidated important concepts in life sciences such as programmed cell death, the Hayflick limit, apoptosis, and death genes. These cases also transformed the material and epistemic practices about the end of cellular life subsequently and led to the formations of new research communities. The four cases together show the ways cell degeneration became a shared subject between molecular cell biology, developmental biology, gerontology, oncology, and pathology of degenerative diseases. These practices and perspectives created a special kind of interconnectivity between different fields and led to a level of interdisciplinarity within cell degeneration research by the early 1990s.
ContributorsJiang, Lijing (Author) / Maienschein, Jane (Thesis advisor) / Laubichler, Manfred (Thesis advisor) / Hurlbut, James (Committee member) / Creath, Richard (Committee member) / White, Michael (Committee member) / Arizona State University (Publisher)
Created2013
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In cancer, various genetic and epigenetic alterations cause cancer cells to hyperproliferate and to bypass the survival and migration mechanisms that typically regulate healthy cells. The focal adhesion kinase (FAK) gene produces FAK, a protein that has been implicated in tumor progression in various cancers. Compared with normal tissue counterparts,

In cancer, various genetic and epigenetic alterations cause cancer cells to hyperproliferate and to bypass the survival and migration mechanisms that typically regulate healthy cells. The focal adhesion kinase (FAK) gene produces FAK, a protein that has been implicated in tumor progression in various cancers. Compared with normal tissue counterparts, FAK is overexpressed in many cancers. FAK is therefore a promising cancer drug target due to its demonstrated role in cancer invasion and metastasis and inhibition of FAK is important to achieve an optimal tumor response. Small molecule FAK inhibitors have been shown to decrease tumor growth and metastasis in several preclinical trials. However, these inhibitors focus narrowly on the enzymatic portion of FAK and neglect its scaffolding function, leaving FAK’s scaffolding of oncogenic drivers intact. Paxillin, a major focal adhesion-associated protein, binds to FAK, enabling it to localize to focal adhesions, and this is essential for FAK’s activation and function. Therefore, disrupting the protein-protein interaction between FAK and paxillin has been hypothesized to prevent tumor progression. The binding of FAK to paxillin at its focal adhesion targeting (FAT) domain is mediated by two highly conserved leucine-rich sequences, the leucine-aspartic acid (LD) motifs LD2 and LD4. The purpose of this project was to develop novel stapled LD2 peptide analogs that target the protein-protein interaction of FAT to LD2. Peptide stapling was performed to enhance the pharmacological performance of the LD2 peptide analogs. Based on the native LD2 peptide sequence, stapled LD2 peptide analogs were developed with the intent to improve efficacy of cell permeability, while maintaining or improving FAK binding. The LD2 peptide analogs were characterized via surface plasmon resonance, fluorescence polarization, immunofluorescence, and circular dichroism spectroscopy. Successful LD2 stapled peptide analogs can be therapeutically relevant inhibitors of the FAT-LD2 protein-protein interaction in cancer and have the potential for greater efficacy in FAK inhibition, proteolytic resistance, and cell permeability, which is key in preventing tumor progression in cancer.
ContributorsNott, Rohini (Author) / Gould, Ian R. (Thesis director) / Marlowe, Timothy A. (Committee member) / Cance, William G. (Committee member) / School of Life Sciences (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
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On 29 June 1988, in Bowen v. Kendrick, the US Supreme Court ruled in a five-to-four decision that the 1981 Adolescent Family Life Act, or AFLA, was constitutional. Under AFLA, the US government could distribute federal funding for abstinence-only sexual education programs, oftentimes given to groups with religious affiliations. As

On 29 June 1988, in Bowen v. Kendrick, the US Supreme Court ruled in a five-to-four decision that the 1981 Adolescent Family Life Act, or AFLA, was constitutional. Under AFLA, the US government could distribute federal funding for abstinence-only sexual education programs, oftentimes given to groups with religious affiliations. As a federal taxpayer, Chan Kendrick challenged the constitutionality of AFLA, claiming it violated the separation of church and state. The Supreme Court found that although AFLA funded programs that aligned with certain religious ideologies, it was constitutional because it did not encourage government involvement in religion, and it held a valid secular purpose in seeking to prevent adolescent pregnancy and premarital sexual relations. By upholding AFLA, Bowen v. Kendrick enabled the US government to continue funding abstinence-only education, which researchers have found to be ineffective.

Created2021-02-26
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Published in 2002, prostate cancer researcher John R. Masters authored a review article HeLa Cells 50 Years On: The Good, The Bad, and The Ugly that described the historical and contemporary context of the HeLa cell line in research in Nature Reviews Cancer. The HeLa cell line was one of

Published in 2002, prostate cancer researcher John R. Masters authored a review article HeLa Cells 50 Years On: The Good, The Bad, and The Ugly that described the historical and contemporary context of the HeLa cell line in research in Nature Reviews Cancer. The HeLa cell line was one of the first documented immortal cell lines, isolated from cervical cancer patient Henrietta Lacks in 1951 at The Johns Hopkins Hospital in Baltimore, Maryland. An immortal cell line is a cluster of cells that continuously multiply on their own outside of the original host. Though the HeLa cell line has contributed to many biomedical research advancements such as the polio vaccine, its usage in research has been controversial for many reasons, including that Lacks was a Black woman who did not knowingly donate her cells to science. In the article “HeLa Cells 50 Years On: The Good, The Bad, and The Ugly,” Masters describes that, despite the benefits of the HeLa cell line, it has caused significant negative impacts on research due to its propensity to contaminate other cell lines, which can potentially invalidate research findings.

Created2021-05-02
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In 2005, Ernest McCulloch and James Till published the article “Perspectives on the Properties of Stem Cells,” which discusses the various properties and future possibilities for the use of stem cells. Stem cells are unspecialized cells that can develop into several different cell types. In the article published in the

In 2005, Ernest McCulloch and James Till published the article “Perspectives on the Properties of Stem Cells,” which discusses the various properties and future possibilities for the use of stem cells. Stem cells are unspecialized cells that can develop into several different cell types. In the article published in the journal Nature on 1 October 2005, the authors say they wrote the article to dispel misconceptions about what stem cells are, what they do, address some controversies surrounding stem cells, and discuss potential uses of stem cells. In the article, McCulloch and Till reveal how stem cell research has revolutionized cancer treatment as well as set the stage for future embryonic and adult stem cell research.

Created2020-06-30
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In “Explaining Recent Declines in Adolescent Pregnancy in the United States: The Contribution of Abstinence and Improved Contraceptive Use,” hereafter “Explaining Recent Declines,” researchers John S. Santelli, Laura Duberstein Lindberg, Lawrence B. Finer, and Susheela Singh discuss what led to the major decline in US adolescent pregnancy rates from 1995

In “Explaining Recent Declines in Adolescent Pregnancy in the United States: The Contribution of Abstinence and Improved Contraceptive Use,” hereafter “Explaining Recent Declines,” researchers John S. Santelli, Laura Duberstein Lindberg, Lawrence B. Finer, and Susheela Singh discuss what led to the major decline in US adolescent pregnancy rates from 1995 to 2002. Working with the Guttmacher Institute, a reproductive health research organization, they found that the decline in US adolescent pregnancy rates between 1995 and 2002 was primarily due to improved contraceptive use. They published their article in 2007 after the US government had increased funding for abstinence-only education between 1998 and 2007. “Explaining Recent Declines” challenged US policies by asserting that there was minimal evidence to support abstinence-only sex education as the primary strategy to prevent adolescent pregnancy.

Created2021-02-15
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The Y-chromosome is one of a pair of chromosomes that determine the genetic sex of individuals in mammals, some insects, and some plants. In the nineteenth and twentieth centuries, the development of new microscopic and molecular techniques, including DNA sequencing, enabled scientists to confirm the hypothesis that chromosomes determine the

The Y-chromosome is one of a pair of chromosomes that determine the genetic sex of individuals in mammals, some insects, and some plants. In the nineteenth and twentieth centuries, the development of new microscopic and molecular techniques, including DNA sequencing, enabled scientists to confirm the hypothesis that chromosomes determine the sex of developing organisms. In an adult organism, the genes on the Y-chromosome help produce the male gamete, the sperm cell. Beginning in the 1980s, many studies of human populations used the Y-chromosome gene sequences to trace paternal lineages. In mammals, the Y-chromosomes contain the master-switch gene for sex determination, called the sex-determining region Y, or the SRY gene in humans. In most normal cases, if a fertilized egg cell, called a zygote, has the SRY gene, the zygote develops into an embryos that has male sex traits. If the zygote lacks the SRY gene or if the SRY gene is defective, the zygote develops into an embryo that has female sex traits.

Created2015-05-28
Description

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in

Thalidomide is a sedative drug introduced to European markets on 1 October 1957 after extensive testing on rodent embryos to ensure its safety. Early laboratory tests in rodent populations showed that pregnant rodents could safely use it, so doctors prescribed Thalidomide to treat morning sickness in pregnant women. However, in humans Thalidomide interfered with embryonic and fetal development in ways not observed in rodent tests. Pregnant women who take Thalidomide are at grater than normal risk for spontaneous abortion and for giving birth to children with developmental anomalies such as shortened, absent, or extra limbs, as well as a variety of heart, ear, and internal organ defects. The failure of rodent models to inform scientists of Thalidomide's teratogenicity in humans ignited debate about the proper use of cross-species testing during drug development.

Created2014-03-07
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Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess

Vitamin A (retinol) is an essential vitamin in the daily functioning of human beings that helps regulate cellular differentiation of epithelial tissue. Studies have shown that an excess of vitamin A can affect embryonic development and result in teratogenesis, or the production of birth defects in a developing embryo. Excess intake of vitamin A and retinoids by pregnant women often results malformations to fetuses' skulls, faces, limbs, eyes, central nervous system. Additionally, doctors often use derivatives of vitamin A, known as retinoids, as medicine to treat a number of skin conditions and carcinomas, the most common form of human cancers.

Created2014-02-28
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Dizhou Tong, also called Ti Chou Tung, studied marine animals and helped introduce and organize experimental embryology in China during the twentieth century. He introduced cellular nuclear transfer technology to the Chinese biological community, developed methods to clone organisms from many marine species, and investigated the role of cytoplasm in

Dizhou Tong, also called Ti Chou Tung, studied marine animals and helped introduce and organize experimental embryology in China during the twentieth century. He introduced cellular nuclear transfer technology to the Chinese biological community, developed methods to clone organisms from many marine species, and investigated the role of cytoplasm in early development. Tong's administrative and scientific leadership in the fields of marine, cellular, and developmental biology contributed to China's experimental embryology research programs.

Created2014-02-18