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Alzheimer’s disease (AD) is characterized by the aberrant accumulation and aggregation of proteins that in turn contribute to learning and memory deficits. The mammalian target of rapamycin (mTOR) plays an essential role in regulating the synthesis and degradation of proteins that contribute to cell growth and learning and memory. Hyperactivity

Alzheimer’s disease (AD) is characterized by the aberrant accumulation and aggregation of proteins that in turn contribute to learning and memory deficits. The mammalian target of rapamycin (mTOR) plays an essential role in regulating the synthesis and degradation of proteins that contribute to cell growth and learning and memory. Hyperactivity of mTOR can cause detrimental effects to protein homeostasis and has been linked to AD. The proline-rich Akt-substrate 40 kDa (PRAS40) is a negative regulator of mTOR, as it binds to mTOR directly, reducing its activity. Upon phosphorylation, PRAS40 detaches from mTOR thereby releasing its inhibitory effects. Increased phosphorylation of PRAS40, and a subsequent increase in mTOR activity has been linked to diabetes, cancer, and other conditions; however, PRAS40’s direct role in the pathogenesis of AD is still unclear. To investigate the role of PRAS40 in AD pathology, we generated a PRAS40 conditional knockout mouse model and, using a neuronal-specific Cre recombinase, selectively removed PRAS40 from APP/PS1 mice. Removing neuronal PRAS40 exacerbated Abeta levels and plaque load but paradoxically had no significant effects on mTOR signaling. Mechanistically, the increase in Abeta pathology was linked to a decrease in autophagy function. Our data highlight a primary role of PRAS40 in the pathogenesis of AD.
ContributorsSurendra, Likith (Author) / Oddo, Salvatore (Thesis director) / Velazquez, Ramon (Committee member) / Pratico, Domenico (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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Breast cancer affects about 12% of women in the US. Arguably, it is one of the most advertised cancers. Mammography became a popular tool of breast cancer screening in the 1970s, and patient-geared guidelines came from the American Cancer Society (ACS) and the US Preventative Task Force (USPSTF). This research

Breast cancer affects about 12% of women in the US. Arguably, it is one of the most advertised cancers. Mammography became a popular tool of breast cancer screening in the 1970s, and patient-geared guidelines came from the American Cancer Society (ACS) and the US Preventative Task Force (USPSTF). This research focuses on ACS guidelines, as they were the earliest as well as the most changed guidelines. Mammography guidelines changed over time due to multiple factors. This research has tracked possible causes of those changes. Research began with an extensive literature search of clinical trials, the New York Times and the Washington Post archives, systematic reviews, ACS and USPSTF archives.

Created2021-02-16
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Science fiction works can reflect the relationship between science and society by telling stories that are set in the future of ethical implications or social consequences of scientific advancements. This thesis investigates how the concept of reproduction is depicted in popular science fiction works.

Created2021-02-10
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By questioning methods of sex selection since their early development, and often discovering that they are unreliable, scientists have increased the creative and technological capacity of the field of reproductive health. The presentation of these methods to the public, via published books on timing methods and company websites for sperm

By questioning methods of sex selection since their early development, and often discovering that they are unreliable, scientists have increased the creative and technological capacity of the field of reproductive health. The presentation of these methods to the public, via published books on timing methods and company websites for sperm sorting, increased interest in, and influence of, sex selection within the global society. The purpose of explaining the history, interest, development, and impact of various sex selection methods in the mid-twentieth century based on the information that is available on them today is to show couples which methods have failed and provide them with the knowledge necessary to make an informed decision on how they choose to go about utilizing methods of sex selection.

Created2021-02-26
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By demonstrating the struggle for sound standard of care for non-medical reproductive health care providers during the nineteenth and early twentieth century, this project emphasizes what the standards of reproductive health care for abortion and contraception might be like if the organizations that made them so readily available, like Planned

By demonstrating the struggle for sound standard of care for non-medical reproductive health care providers during the nineteenth and early twentieth century, this project emphasizes what the standards of reproductive health care for abortion and contraception might be like if the organizations that made them so readily available, like Planned Parenthood, were defunded or criminalized in our modern setting.

Created2021-02-23