Matching Items (42)
Description
Midlife is a unique period of development during which individuals are simultaneously engaging in multiple roles. Despite this, there is a surprisingly small amount of research on this period of the life course. In order to examine sources of adversity during this period, we analyzed interviews with individuals in midlife about their greatest challenge. The most common themes for types of adversity included relationships, health, and work, reflecting the unique combination of roles in midlife.
ContributorsMattern, Cameron Michele (Author) / Infurna, Frank (Thesis director) / Corbin, William (Committee member) / Grimm, Kevin (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
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
Description
The mammalian target of rapamycin (mTOR) is integral in regulating cell growth as it maintains a homeostatic balance of proteins by modulating their synthesis and degradation. In the brain, mTOR regulates protein-driven neuroplastic changes that modulate learning and memory. Nevertheless, upregulation of mTOR can cause detrimental effect in spatial memory and synaptic plasticity. The proline-rich Akt-substrate 40 kDa (PRAS40) is a key negative regulator of mTOR, as it binds mTOR and directly reduces its activity. To investigate the role of PRAS40 on learning and memory, we generated a transgenic mouse model in which we used the tetracycline-off system to regulate the expression of PRAS40 specifically in neurons of the hippocampus. After induction, we found that mice overexpressing PRAS40 performed better than control mice in the Morris Water Maze behavioral test. We further show that the improvement in memory was associated with a decrease in mTOR signaling, an increase in dendritic spines in hippocampal pyramidal neurons, and an increase in the levels of brain-derived neurotrophic factor (BDNF), a neurotrophin necessary for learning and memory. This is the first evidence that shows that increasing PRAS40 in the mouse brain enhances learning and memory deficits.
ContributorsSarette, Patrick William (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Kelleher, Raymond (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
In previous research, Luthar and Barkin (2012) found that across three different samples collected from three high-achieving schools, adolescents reported elevated rates of maladjustment behaviors, which include substance use, and internalizing and externalizing symptoms. Additionally, past research has also indicated that these maladjustment behaviors are related to parent relationships. A group of high-achieving adolescents that research has not yet focused on are those attending boarding schools, who may have higher-quality relationships with parents due to less daily strife. This study aimed to examine high-achieving adolescents across five samples from five high schools, two of which were boarding schools. This study hypothesized that the high-achieving adolescents attending both boarding schools would report lower rates of substance use, internalizing and externalizing symptoms, and lower rates of perceived parent criticism and expectations in comparison to those attending the day schools. Substance use, internalizing and externalizing symptoms, and parent relationships were measured using self-report measures that were completed by students attending these schools. Results showed that both boarding schools reported elevated rates of substance use in comparison to the three day schools and these rates measured above national norms. At the same time, both boarding schools reported lower rates of internalizing and externalizing symptoms when compared to rates reported by the day school students. This study also found that there were differences among parent relationship measures, such as criticism and expectations, among all school samples. Results of this study also showed that aspects of parent relationship, such as parent knowledge, were associated with rates of substance use among all school samples. In summary, boarding school students showed elevated substance use, similar parental relationship quality, and lower mental health symptoms compared to day school students. For all students, some aspects of the parental relationship were related to levels of substance use.
ContributorsTaracena, Emily Gabriella (Author) / Luthar, Suniya (Thesis director) / Infurna, Frank (Committee member) / Davis, Mary (Committee member) / Division of Teacher Preparation (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
To date, it has been difficult to elucidate the role of tau in learning and memory during adulthood due to developmental compensation of other microtubule associated proteins in Tau knockout (KO) mice. Here, we generated an adeno-associated virus (AAV) expressing a doxycycline (doxy)-inducible short-hairpin (sh) RNA targeted to tau, and stereotaxically and bilaterally injected 7-month-old C57BL/6 mice with either the AAV-shRNAtau or an AAV expressing a scramble shRNA sequence. Seven days after the injections, all animals were administered doxy for thirty-five days to induce expression of shRNAs, after which they were tested in the open field, rotarod and Morris water maze (MWM) to assess anxiety like behavior, motor coordination and spatial reference memory, respectively. Our results show that reducing tau in the adult hippocampus produces significant impairments in motor coordination, endurance and spatial memory. Tissue analyses shows that tau knockdown reduces hippocampal dendritic spine density and the levels of BDNF and synaptophysin, two proteins involved in memory formation and plasticity. Our approach circumvents the developmental compensation issues observed in Tau KO models and shows that reducing tau levels during adulthood impairs cognition.
ContributorsTran, An Le (Author) / Oddo, Salvatore (Thesis director) / Velazquez, Ramon (Committee member) / Roberson, Erik (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The literature has consistently established levels of adolescent maladjustment well above national norms for both socioeconomic (SES) extremes (Lyman & Luthar 2014). Yet literature on positive adolescent adjustment, and its protective or even corrective factors is lacking (Eisenberg, Zhou, & Coller, 2001). This study examined the effects of gender and SES on parent attachment in relation to reports of prosocial behavior. Eleventh grade adolescents (N = 397) were recruited from two public high schools for academically-gifted students who were either high or low-level SES (i.e. the extremes). The students provided passive consent and answered questions on their demographics, perceived relationship with their parents, and tendency to behave in a prosocial manner. Multivariate analyses of variance and follow up analyses of variance were run by gender and SES to determine main effects for gender and SES on parent attachment and prosocial behavior. Regressions following preliminary correlations analyzed whether parental attachment predicted higher levels of adolescent prosocial behavior. Results demonstrated that females communicated with their mothers significantly more and reported higher levels of prosocial behavior than their male counterparts. Findings with regard to SES revealed that high SES adolescents reported increased parent attachment, whereas low SES adolescents reported higher levels of community\u2014based prosocial behaviors. Finally, certain dimensions of parent attachment predicted increases and decreases only in specific prosocial behaviors. Because prosocial behaviors change throughout adolescence, future ventures should consider a longitudinal analysis to obtain a more comprehensive picture of adolescent positive adjustment.
ContributorsAli, Hira (Author) / Luthar, Suniya (Thesis director) / Infurna, Frank (Committee member) / Davis, Mary (Committee member) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Depression, anxiety, and suicidal thoughts or actions are on the rise in adolescents (National Institute of Mental Health, 2015; Bridge, Asti, & Horowitz, 2015). Parents, school administrators, and therapists are searching for resiliency factors with in at-risk groups to aid students in need. In previous work, Luthar and Zigler (1992) reported that intelligent youth are more resilient than less intelligent youth under low stress conditions but they lose their advantage under high stress conditions. This study examined whether intelligence (reflected in grade point average; GPA) and maladaptive (internalizing and externalizing symptoms) behaviors are negatively related in adolescents, and tested whether level of stress, reflected in emotion regulation and friendship quality, moderated that association. It also probed whether the relationships differ by gender. Sixth-graders (N=506) were recruited with active parental consent from three middle schools. Adolescents completed self-report questionnaires Regarding demo graphics, maladaptive behaviors, emotion regulation, and friendship quality, and GPA data were collected from the school. Regression analyses found that GPA was negatively related to externalizing symptoms. Girls with poor friendship communication report significantly higher maladaptive behaviors. This relation was more pronounced for girls with high GPAs, as predicted. Results support the theory that intelligent female adolescents are more reactive under adverse circumstances. Future efforts should follow students through middle school into high school to evaluate whether friendships remain important to adjustment, hold for boys as well as girls, and have implications for relationship interventions.
ContributorsGonzales, Ashlyn Carol (Author) / Luthar, Suniya (Thesis director) / Davis, Mary (Committee member) / Infurna, Frank (Committee member) / Department of Psychology (Contributor) / Sanford School of Social and Family Dynamics (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
The aims of this project are: (i) to identify structural and molecular changes in the brains of 3xTg-AD mice and (ii) to determine whether decreasing S6K1 protects the brain from these changes. To achieve our goals, we decided to remove one copy of the S6K1 gene in 3xTg-AD mice by breeding them with S6K1 knockout mice (S6K1+/-). In previous studies, we have seen that reducing S6K1 levels in 3xTg-AD mice improved spatial memory and synaptic plasticity which was associated with reduced A and tau pathology. Here, we used a multiparametric MRI to assess volumetric and blood flow changes in the brain of 20-month-old 3xTg-AD mice. We found that 3xTg-AD/S6K1+/- mice had higher blood flow and cortical volume compared to 3xTg-AD mice. However, we saw no significant differences between 3xTg-AD mice and NonTg mice. We further found A levels and plaque numbers were significantly lower in 3xTg-AD/S6K1+/- mice compared to 3xTg-AD mice. This reduction in plaques could account for the improvement in blood flow in 3xTg-AD/S6K1+/- mice. To try to understand the reason behind the increase in cortical volume in the 3xTg-AD/S6K1+/- when compared to the 3xTg-AD, we measured markers of synaptic density, PSD95, and synaptophysin. We found that PSD95 levels were not different between the four groups. However, synaptophysin levels were significantly lower in 3xTg-AD mice compared to NonTg levels and returned to baseline levels in 3xTg-AD mice lacking one copy of the S6K1 gene. This difference in synaptophysin could explain, at least in part, the difference in volume between the four groups analyzed. Overall, this represents the first evidence showing that reducing mTOR signaling improves blood flow and cortical volume in a mouse model of AD.
ContributorsShukla, Prakriti (Author) / Oddo, Salvatore (Thesis director) / Caccamo, Antonella (Committee member) / Jankowsky, Joanna (Committee member) / School of Molecular Sciences (Contributor) / School of Public Affairs (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Currently, many patients suffer from post-circumcision complications caused by poor patient selection and/or poor technique of the practicing physician. In addition, the majority of medical practitioners are incapable of/unwilling to conduct specific circumcision procedures on their patients. In the end, this either results in unsatisfied patient families, who unwillingly have their children circumcised using methods contrary to their belief, or results in individuals who are not certified practitioners of medicine conducting the procedures, greatly increasing the risk of the patients experiencing preventable complications. In order to locally address the aforementioned problems, this thesis committee, consisting of Dr. Frank Infurna, Dr. Justin Ryan, and Dr. Zachary Zuniga, and I, developed a training module that standardized the instruction that interns, residents, attendings, fellows, hospitalists, and other interested physicians will receive regarding neonatal circumcision at Phoenix Children's Hospital. To begin, the pre-operative, intra-operative, and post-operative procedures related to the Gomco clamp neonatal circumcision procedure were heavily researched using literature sourced from library databases and consultation of specialists, such as Dr. Zuniga. Given that the training was developed to instruct individuals within the medical field, the material was then truncated to promote succinctness and specificity towards the targeted population. In order to convey the specific techniques that are clinically preferred to be used in the procedure, one of Dr. Zuniga's Gomco clamp neonatal circumcision procedures was recorded and converted into GIFs, with each GIF depicting a specific technique of the procedure. The aforementioned materials were then arranged into a slide deck in order to mitigate the need for future training facilitators to tamper with the material in the process of creating visuals to be used during the training. Given the sensitivity of the material included in the slide deck, it will only be available for use on Phoenix Children's Hospital premises. To incorporate instruction regarding both the traditional (Gomco clamp) and religiously-preferred circumcision techniques into the training module, appointments, consisting of discussions regarding the procedural, cultural, and social facets that must be taken into consideration when conducting a circumcision procedure on a patient from a Muslim family, were set-up with pediatric physicians, currently practicing in Abu Dhabi, United Arab Emirates, who have specialized knowledge of conducting circumcisions in the Middle East. Since Brit Milah, the Jewish circumcision ceremony, is, unlike in Islam, required to be conducted by a Mohel in either a synagogue or house, it was not covered as holistically as "Khtan", Islamic circumcision, which is less heavily regulated. Thus far, the training module has been piloted twice, once with a group of medical students and physicians and once with medical education program directors and instructors. The critique from both sessions has been used to prepare the material for use in neonatal circumcision training sessions that will be introduced in clerkship and residency curriculum. In the future, the results of this implementation can be used to prepare the module for submission to the American Academy of Pediatrics to be made a prerequisite for physicians to undergo before conducting neonatal circumcisions.
ContributorsMeraban, Amir Reza (Author) / Infurna, Frank (Thesis director) / Ryan, Justin (Committee member) / Zuniga, Zachary (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The mammalian olfactory system is commonly studied by using the mouse as a model system. Odor habituation is used to investigate odor perception and learning processes. Most previous experimental preparations have been tedious, requiring a researcher to manually change odorants, record investigation time and duration at each odorant, or physical alteration on the mice to enable video tracking. These limitations were overcame by creating an odorized hole-board to allow for systematic and automatic recording of olfactory behavior in mice. A cohort of five male mice were utilized in these experiments and the responses to the odor of strawberries, a diet staple of wile mice, were examined. Experiment 1 showed that free-feeding mice exhibit a preference to locations with strawberry (over control locations), even when these locations can only be identified using olfaction. This preference habituates within a trial but not across days. Experiment 2 showed that strawberry odor without reward causes habituation or extinction to the odor both within trials and across days. From these experiments, it can be concluded that mice innately explore strawberry odor and this can be exploited to the study odor habituation using an odorized hole-board.
ContributorsMa, Jason (Author) / Smith, Brian (Thesis director) / Gerkin, Richard (Committee member) / Oddo, Salvatore (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12