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Supporting Data for: Effect of Cation-pi Interactions on the Phase Behavior and Viscoelastic Properties of Polyelectrolyte Complexes
No full textThis dataset contains thermogravimetric analysis (TGA) profiles, turbidity data, and nuclear magnetic resonance (NMR) spectra of samples of poly(styrene sulfonate), poly(diallyldimethylammonium), and poly(2-acrylamido-2-methyl-1-propanesulfonic acid) prepared with lithium bromide, sodium bromide, and/or potassium bromide, and water, reported in the authors' manuscript "Effect of Cation-pi Interactions on the Phase Behavior and Viscoelastic Properties of Polyelectrolyte Complexes.
Writing GenQ
No full textA creative writing workshop designed to foster intergenerational dialogue within the LGBTQ communit
A New Perspective on DEIB Work in Global Education
No full textAs the University Center for International Studies (UCIS) supports students in embracing the world, we do so with the understanding that the world is a complicated place and students come to Pitt with diverse backgrounds and ways of relating to the world. As part of a broader Diversity, Equity, Inclusion, and Belonging Initiative at UCIS, for the Year of Discourse and Dialogue UCIS unit collaborated on developing programs and a framework for incorporating student perspectives into making Pitt a more inclusive and welcoming space for global learning. The project involved two inter-related series: Series One - Decolonizing International Studies and Global Education, and Series Two - Rapid Response to Global Events
Anna May Wong: Dialogues about an Asian American Life in Film
No full textPoster for Year of Discourse and Dialogue April 202
American Civic Education and Literacy Initiative
No full textThe American Civic Education and Literacy Initiative (ACE) is a multi-year collaborative effort between the University of Pittsburgh at Johnstown, local school districts in the Johnstown region, and state and national civics advocacy organizations. The ACE Initiative hosted a teacher professional development day in October 2023 that welcomed over 70 teachers from 12 school districts. ACE also hosted an event known as the "Democracy Bowl" in April of 2024 that included 130 student and teacher participants in a trivia competition and celebration of service-learning projects for grades 6-12 from 11 school districts. Representatives of various civic organizations were on hand to judge and assist with the events and to meet with one another
Regulation of Myeloid Cell Function and Inflammation by Interferon λ During Pulmonary Super-Infection
No full textInfluenza infections represent a significant cause of death annually, caused by both seasonal and pandemic strains of the virus. While many hospitalizations and mortalities occur in individuals with comorbidities, recovery from primary influenza infection can be complicated or prolonged by secondary bacterial infection, commonly caused by methicillin-resistant Staphylococcus aureus (MRSA). The higher mortality rates and prevalence of super-infection makes understanding mechanisms by which super-infection is worsened and prolonged of the utmost importance. Interferon λs (IFNλs), which are produced highly during influenza infection, have been studied for their dual anti-viral and anti-inflammatory nature. Studies have shown that IFNλs restrict viral replication without over-activation of inflammatory responses against both influenza and SARS-CoV-2. However, newer data has uncovered several mechanisms by which IFNλ may worsen super-infection, including suppression of bacterial uptake by neutrophils and epithelial cell repair. These data are in line with work from our laboratory, showing suppression of type 17 immune responses and bacterial clearance during secondary MRSA infection by type I IFNs. Based on these data, I sought to elucidate the impact that IFNλ has on immune cells during super-infection to potentially better inform clinical use of IFNλ during respiratory viral infections. To this end, I employed the use of multiple mouse models to deplete the IFNλ receptor (IFNLR1) from various cell types. I found that depletion of IFNLR1 in all cells enhanced bacterial uptake by phagocytes, leading to increased bacterial clearance and reduced inflammation, while more specific IFNLR1 deletion in myeloid cells, including interstitial macrophages, lung monocytes,
and inflammatory monocytes, enhanced the localization of bacterial within acidic phagolysosomes. Interestingly, IL-17 and IL-22 production were increased in global IFNLR1-/- mice while their upstream activators, IL-6, IL-23, and IL-1β, did not follow the same pattern. Based on this observation, I further investigated how alteration of IL-1 impacted bacterial clearance and whether this function was IFNλ-dependent. Modulation of both IL-1α and IL-1β showed that only IL-1β influenced bacterial clearance through enhanced neutrophil recruitment and AMP production, which was IFNλ-independent. The studies presented herein contribute further knowledge to how IFNλ impacts immune cell populations during super-infection and uncover new avenues for further study
A MOLECULAR AND COMPUTATIONAL APPROACH TO ANALYZE THE BIOGENESIS OF THE POTASSIUM-CHLORIDE COTRANSPORTER 2 (KCC2), A NEURON-SPECIFIC PROTEIN IMPLICATED IN DISEASE
No full textThe concentration of intracellular and extracellular potassium is tightly regulated due to the action of various ion transporters which play vital roles in all organs and cell types. Unsurprisingly, defects in the biogenesis, function, and/or regulation of these proteins are linked to a range of catastrophic human diseases. The neuron-specific potassium chloride co-transporter 2 (KCC2) is critical for brain development and regulates γ-aminobutyric acid-dependent inhibitory neurotransmission. KCC2 dysregulation is implicated in neurodevelopmental disorders, including schizophrenia, autism, and epilepsy. Based on its complex architecture and function, reduced cell surface expression and/or activity have been reported when some disease-associated mutations are
present in the gene encoding the protein, SLC12A5. These data suggest that KCC2 might be inherently unstable, thus making it susceptible to cellular quality control pathways that degrade
misfolded proteins. For my dissertation research, I sought to explore the protein quality control mechanisms that regulate KCC2 and characterize select mutants that have been implicated in disease.
In this thesis, I begin by reviewing the disease relevance, structure, and protein quality control pathways that regulate potassium transporters in the cell. From here, I report my endeavors to examine KCC2 stability and/or maturation in five model systems: yeast, HEK293 cells, primary rat neurons, and rat and human brain synaptosomes. This work details the first comparison into the influence that the cellular and membrane environments have on several fundamental KCC2 properties. I also acknowledge the advantages and disadvantages of each system to set the stage for the investigation of select KCC2 disease-associated mutations expressed in HEK293 cells. In
this next area of study, I identify which KCC2 mutants are maturation-defective and are depleted from the cell surface. To determine whether KCC2 maturation could be predicted, I then employed three computational pathogenicity predictors. Indeed, a pathogenicity score using one program, Rhapsody, correlates with defects in KCC2 ER-to-Golgi transport, and this algorithm
outperformed two other pathogenicity predictors. These data demonstrate that a bioinformatic tool can predict the efficiency of ER exit and can be used to develop hypotheses on defects associated with other disease-associated SLC12A5 alleles as they are identified
Vaccine Effectiveness Against Influenza-Associated Hospitalizations in Adults with Liver Disease
No full textBackground. Influenza causes 100,000–710,000 hospitalizations annually in the U.S. Patients with liver disease are at higher risk of severe outcomes following influenza infection. This study evaluated vaccine effectiveness (VE) against influenza-associated hospitalization among adults with liver disease.
Methods. Data from the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN), a test-negative case-control study, from 2015 to 2020 was used to estimate VE among adults ≥18 years admitted for acute respiratory illness (ARI). VE was calculated as (1-adjusted odds ratio)*100%, comparing the odds of vaccine receipt between laboratory-confirmed influenza cases and test-negative controls using a multivariable logistic regression model with inverse probability of treatment weighting (IPTW). The model was adjusted for age, sex, race/ethnicity, study site, presence of immunocompromising condition, date of illness onset, days from illness onset to specimen collection, presence of liver disease, and the interaction between liver disease and vaccination.
Results. In total, 1,622 (12.8%) of 12,704 adults hospitalized for ARI had ≥1 liver disease(s). Compared with those without liver disease, adults with liver disease were more likely to be admitted to the ICU (15.7% vs 12.8%, P = .001) or to die in hospital (3.0% vs 1.4%, P < .001). The IPTW-adjusted VE against influenza-associated hospitalization was 27% (95% confidence interval [CI], 22–32%) among patients without liver disease, but the VE of 11% (95% CI, -8–26) was not significant among those with liver disease. Significant effect modification of VE by the presence of liver disease was found (P < .05 for interaction term between liver disease and vaccination).
Conclusion. While influenza vaccination significantly reduced the risk of influenza-associated hospitalization among adults without liver disease, the protective effect was not significant among those with liver disease. Further studies are warranted to evaluate influenza VE in patients with different types of liver disease and other methods to protect these vulnerable patients from ARI-related hospitalization. Our study underscores the public health importance of optimizing the influenza immunization strategy for patients living with liver disease
Evaluating liposomes as carriers to retain agricultural nitrogen fertilizer
No full textLiposomes are microscale (0.025 – 2.5 um diameter) lipid vesicles that are used to deliver drugs to specific areas of the human body. Liposomes can also deliver nutrients to plants, possibly more efficiently than traditional fertilizers, which could reduce nitrogen (N) losses and improve overall N use efficiency on farms. However, because liposomes are composed of carbon (C), they may serve as a C source for soil microbes, stimulating unintended microbial activity. This increased microbial activity may, in turn, enhance biogeochemical cycling and impact the availability of encapsulated nutrients to crops. To assess the possible impacts of using liposomes as carriers for N, this study quantifies the effect of liposomes on soil C and N cycles in the absence of plants. We conducted an incubation experiment using agricultural soil from USDA LTAR no-till corn plots in Pennsylvania Furnace, PA. Soils were treated with C (aqueous empty liposomes (EL) or glucose), N (aqueous KNO3), or coupled C+N (N loaded liposomes (NL), EL + KNO3, or glucose + KNO3) additions. Water was added as the control treatment. The concentration of CO2 in the vial headspace was measured over the 7-day incubation period to determine potential C mineralization rates. Initial and final exchangeable nitrate (NO3--N) and ammonium (NH4+-N) in the soil were measured to determine potential nitrification and N mineralization rates. Nitrous oxide (N2O) concentrations were also measured to examine N losses from denitrification. Our results show similar increased potential C mineralization rates of soil treated with NL and EL (46.2 ± 1.7 and 40.7 ± 3.3 mg C kg-1 dry soil day-1, respectively) relative to the control (8.26 ± 0.96 mg C kg-1 dry soil day-1). Liposome treatments, NL and EL, had net losses of NO3--N, while the control varied little during the 7-day incubation. A peak in N2O concentrations on day 1 in liposome treated soils suggested rapid denitrification. These findings indicate that soil microbes can utilize liposomes as a C source to drive rapid N immobilization, which can ultimately reduce N leaching losses in farm fields
Technologies of control and the condition of being-plugged-in: resituating Nozick’s experience machine through Heidegger, Kant, and Arendt
No full textThis paper explores how technology can be viewed as more than just an instrument and how this conceptual reframing reveals various ways in which our thoughts, behaviors, and the realm of human affairs as a whole are acted upon and significantly altered. Through the process of setting up Nozick's (2006, 2013) experience machine as an analogy for technology, we can observe the ways technology acts on us epistemically and ontologically, and how the technological mediation of experience isn't something that need be reserved for a hypothetical. Instead, this paper charts this mediation as occurring throughout history and becoming more frequent in its occurrence — we've been plugging-in for millennia and the recent trends indicate the movement towards a state of living where plugging-out is no longer an option — and this comes with drastic changes to our understandings of autonomy, agency, and freedom, and with even greater implications for the near future. The extension of this analogy reveals multiple conceptual tools that can assist in our discussions regarding human-machine relations, such as the different types of plugging-in (nascent, primary, secondary, intermediary), how this has historically developed and the continuum that can be drawn from it, the endpoint of being locked into the condition, concepts like phenomenological alienation, tethered freedom, and doptography that arise through deeper investigations into these relations, and how these challenge key Western accounts of freedom