Pittsburgh Undergraduate Review

Identifying how drug efflux mechanisms impact Acinetobacter baumannii evolutionary paths to ciprofloxacin resistance

2024-07-31T21:31:01-04:00

Acinetobacter baumannii is a multi-drug resistant pathogen commonly found in clinical settings. This pathogen frequently uses efflux pumps to mitigate antibiotic treatment stress and eliminate the drug. When A. baumannii is exposed to antibiotics, it often develops mutations in the efflux pump regulator genes, causing an increase in efflux pump production. We hypothesize that efflux is a key pathway that leads to treatment failure in A. baumannii infections. The extent to which increasing drug efflux impacts other cellular functions remains unknown. To identify how efflux pump mutations impact growth, resistance, and evolvability, wildtype A. baumannii laboratory strain 17978UN, along with four mutants of this strain, each with a single nucleotide polymorphism (SNP) in an efflux pump regulator (adeL L341R, adeN I49N, adeR D23Y, and adeS R152S), were propagated in the presence of antibiotic and an efflux pump inhibitor to place selective pressure on the isolates. SNPs increase the production of efflux pumps; inhibiting efflux ability will determine if the effect of each SNP is nullified. All evolved populations demonstrated differences in fitness and antibiotic resistance in comparison to their respective ancestors; the extent of adaptation affecting each phenotype was highly dependent on the regulator that was mutated. Counterintuitively, efflux inhibitors also placed stress on wild-type A. baumannii which leads to antibiotic resistance. These results demonstrate that efflux regulator mutations can influence population adaptability and cause treatment failure. Understanding the role that different efflux systems play in treatment failure and drug resistance evolution will be instrumental in developing treatment strategies that hinder the development of antibiotic resistance.

Contextual Fear Conditioning Uncovers Spine and Learning Deficits in the Retrosplenial Cortex in a Familial Alzheimer’s Disease Mouse Model

2024-08-03T14:40:03-04:00

While excitatory synapse loss is documented in the brains of Alzheimer’s Disease (AD) patients, its role in episodic learning decline, one of the first evident AD symptoms, is unclear. The retrosplenial cortex (RSC), a cortical structure required for episodic learning, provides an ideal entry point to study the role of synapse loss in cognitive decline in AD since it is a site of high amyloid load and dysfunctional early in AD progression. Further, excitatory synapse assembly, both turnover and clustered synapse formation, is highly correlated with episodic learning performance in the RSC. We hypothesize alterations in synapse assembly in the RSC of AD patients contribute to early cognitive decline in the disease. To address this hypothesis, we examined both excitatory synapse density in the RSC and contextual learning in a familial AD (fAD) mouse model, an early onset amyloid model of AD. Importantly, we find age-dependent excitatory synapse loss in the RSC of fAD mice, as measured by imaging and quantification of GFP-labeled dendritic spines. Further, prior to frank spine loss in 5-month-old fAD mice we found episodic learning deficits, as measured by contextual fear conditioning (CFC). Using this early time point, we examined spine dynamics in vivo with MP imaging in the RSC of fAD mice or controls while engaged in CFC learning. Interestingly, we find deficits both in spine turnover and clustered spine formation and a loss of correlations of these spine metrics with CFC performance, suggesting aberrant spine dynamics may be causal in episodic learning deficits in this AD model, consistent with our hypothesis. Future studies will pharmacologically target these aberrant spine dynamics in fAD mice in an effort to strengthen the causal link between alterations in synapse assembly and cognitive decline in AD as well as provide potential therapeutic approaches to reverse early stages of the disease.

How Social Identities Facilitate the Growth of Affective Political Polarization

2024-08-22T10:58:16-04:00

This study explored the relationships between a selection of social identity factors and affective political polarization among adults in the United States. A broad selection of literature was reviewed and employed in informing a descriptive and inferential statistical analysis of 2008 and 2020 American National Election Studies (ANES) survey data. Multiple regression was used to describe and quantify the relationships between selected variables and affective polarization within the datasets. These methods were paired with tests for differences in means in a comparative analysis of the 2008 and 2020 demographic and political environments, which revealed a statistically significant difference in the levels of affective polarization between the two years. Ideological polarization and ageing stood out as the factors that contributed most heavily to this this growth in affective polarization. Broadly, these findings suggested that demographic and psychographic shifts may have played a role in facilitating growth of affective political polarization across the years. Finally, a post-hoc analysis identified the growth of affective polarization as originating from increased hostility for political out-groups, highlighting the need for further research into other political, social, and economic events that may have triggered the growth of affective polarization.

Quantitative Measurements of the Effect of Framing and Social Closeness on Decision Making

2024-08-03T14:39:01-04:00

According to prospect theory of framing, people's decisions are influenced by the potential outcomes themselves and how those outcomes are framed. In our study we investigated if social closeness would influence people in the same way and if it has an increased impact when used in combination with framing. We hypothesized that if the message is in gain-frame, then the potential donors, participants, will be more willing to donate, and if the potential donor and the recipient have a close relationship, then the donor will show higher willingness to donate. Furthermore, it is hypothesized that there will be an interaction effect between message framing and social closeness on willingness to donate. Participants (N = 1539) were randomly assigned to two different types of survey, one in a gain frame and other one in a loss frame. Social closeness was manipulated into two levels, close family member and close friend, and participants were again randomly assigned to two different types, with one asking to give the name of their close friend, and the other one asking to give the name of their close family member. Framing and social closeness both had effects on participants' decision making, however, unlike our hypothesis, did not have a combined effect. Our results imply that individuals may process information about framing and their social relations separately when deciding on donating. The cognitive process involved in this kind of decision making may require two separate processes for evaluating framing and social closeness, respectively.

Love Tree

2024-08-21T19:00:10-04:00

Judas Iscariot awakes in the ninth circle of hell, confused yet assured of his belonging there. He experiences multiple different realities simultaneously as he attempts to grapple with his situation and former life—a counternarrative focusing on the created realities of literature and legacies for fictional and religious characters.

Comparing a Microprocessor to the Brain: Exploring Knowledge, Intelligence, and Consciousness in an Age of Artificial Intelligence

2024-08-03T14:38:25-04:00

Brains and microprocessors, while seemingly distinct, share a profound complexity that challenges our understanding of both. In "Could a Neuroscientist Understand a Microprocessor?" by Eric Jonas and Konrad Paul Kording, this complexity is explored through a comparative analysis, raising questions about knowledge, complexity, and the relationship between humans and machines. The authors challenge the common analogy of brains as nature's computers, highlighting the struggle neuroscientists face in comprehending systems like microprocessors, despite their similar composition of billions of interconnected components. Jonas and Kording argue that the limitations of current neuroscience frameworks hinder a deep understanding of brain function, suggesting that methodologies from computer science could enhance the field. Their critique extends to fundamental philosophical debates about consciousness and intelligence, questioning what the difficulties in understanding complex systems reveal about the nature of knowledge. This essay dissects these limitations and their impact on our understanding of brain processes, advocating for an interdisciplinary approach to intelligence that encompasses both biological and artificial systems. By embracing the parallels between brains and microprocessors, we can advance a more comprehensive understanding of both.

Sculpting Civilizations: The Influence of Artwork in the Maintenance of Ancient Cities

2024-08-03T14:39:34-04:00

The role of art in the development of urban life is an important topic relating to communication, creativity, and the Great Traditions of urbanism. Art is a necessary way to communicate ideals and traditions; for example, stained glass in orthodox churches is used as an alternative to the Bible to teach the illiterate the stories about orthodox religion. Trends in art forms, styles, and subject could indicate a lot about urban values and how these values change over time as cities develop. This free range of expression gives insight into what city populations valued. Styles reveal how conservative a community is, or what mindsets and way of thinking people have. For instance, abstract styles tell us about the more scattered ways people approach issues and themes, while something like pop art can tell us about the value of cultural revolution and a progressive mindset. Art, particularly public art, illuminates political ideologies, inequalities, public consciousness, narratives, and religions. The study of urban art can also simply help us visualize and recreate what experiencing a city is like in the viewpoint of the citizens living there. Through a close analysis of the impact of artwork in Ancient Egypt and Ancient China, we can see which famous theories on the development on ancient cities can be applied to explain the role of art in its maintenance.

Journey to the East: Faculty Spotlight with Michael Meyer

2024-11-07T20:12:56-05:00

A spotlight on Professor Michael Meyer.