University at Albany, State University of New York
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Synthesis of Small Molecules as Therapeutic Candidates
Get PDFRNA plays a critical role in many biological functions, such as normal cellular functions or disease-related processes. Regulating biological processes through RNA-based therapeutics can be employed by the reversible photoregulation of oligonucleotides. Azobenzene, a light-responsive compound that changes conformation when exposed to ultraviolet (UV) or visible light, is attached to cytidine phosphoramidite to be incorporated in a series of RNA oligonucleotides. The reversibility of the nucleoside and oligonucleotide is verified through UV melting point experiments. The modified oligonucleotide can change conformation upon light irradiation to stop reverse transcription (RT) in the presence of many different reverse transcriptase enzymes. This technique can be used to optically control RNA structures and functions for gene therapy by limiting off-target effects. A redshifted azobenzene could be explored for safer biological applications using longer wavelengths of light.
Myotonic Dystrophy Type 1 (DM1) is a genetic disorder caused by expanded CTG repeats in the DMPK gene, leading to the sequestration of Muscleblind-like (MBNL) protein. The sequestration of this protein disrupts RNA splicing. Small molecules are emerging as promising drug candidates specifically polycyclic compounds in recently approved FDA pharmaceuticals. In this study, the use of modified polycyclic compounds (MPCs) is being explored as a splicing modulator. The MPC targets the toxic CUG repeat-expanded RNA, thereby rescuing MBNL proteins and restoring correct RNA processing. The synthetic route, purification, and characterization in our symmetrical benzoxazole MPC is being studied for its possible solubility advantages in aqueous solutions
Cellular Senescence and the Remediation of Salivary Gland Function via Nanoparticle Delivery Models
No full textCellular senescence is known to be a root cause of multiple aging related diseases, as the cells are under permanent cell cycle arrest and therefore can no longer replicate. Affected cells produce a senescence-associated secretory phenotype (SASP) response, signaling to nearby cells that they are under this condition. A variety of molecules are released and expressed under this SASP response, including cytokines, chemokines, proteases, and growth factors. These molecules contribute to moderate inflammation, induction of fibrosis, and the creation of new senescent cells due to the bystander effect. Currently, two main classifications of drugs are employed to remedy cases where cellular senescence is causing tissue dysfunction. Senolytic drugs act to eliminate senescent cells from the body which can provide relief and delay the aging process, whereas senomorphic drugs work to inhibit the release of SASP factors into the surrounding environment, decreasing the spread of senescence within tissues to improve organ function and reduce inflammation. The SASP of senescent cells is modulated by a series of microRNAs (miRNAs), contributing to key factors of the phenotype such as permanently stabilizing cell cycle arrest, suppression of proteins, acceleration of the senescence process, and bolstering inflammation to the surrounding area. These miRNAs of interest can then be targeted by senescence associated drugs, and antagomirs (anti-miRs) can be delivered into senescent cells with the assistance of iron nanoparticles for therapeutic purposes. This thesis seeks to establish consistent methods of detecting and inducing senescence, and additionally, devise a strategy for the delivery of iron nanoparticle constructs into senescent cells. Obtaining a greater understanding of the senescence process and the chemical makeup of the SASP can accelerate the development of innovative and novel therapeutic options for affected individuals
Worldbuilding a Queer Before: D&D as a Neomedievalism for a Modern Age
Get PDFDungeons & Dragons (D&D) has had countless participants and audience members in the course of its over fifty-year existence. It has also been the subject of several studies that attempt to capture its unique form of performative play. Yet, there has been a scarcity of scholarship on how D&D acts as a neomedievalism and how that can offer a queer kind of opportunity to its players, allowing them to find a place in a past that is historically inaccessible and yet endlessly in the process of being (re)imagined. Using an interweaving of archival theory with queer and performance studies, particularly in regard to José Esteban Muñoz’s conceptions of queer utopia and futurity, this thesis will seek to explore what is remembered, what is forgotten, and how play can help to rethink the boundaries between these two points. Here, the problematics of history-making entwine with the possibilities presented by ‘playing queer,’ a style of gameplay that allows individuals to rewrite the rules dictating the narrativity and performativity of the game and of their own lives. D&D, in its emphasis on both the individual experience of identity and the collaborative imagination at its core, gives its participants the chance to remake their expectations of their own world and of all the worlds that came before. Through the window it provides into the potential of the medieval, D&D shows us how a transtemporal queer and trans community across time is only a touch away—all it takes is a roll of the dice
Light-Driven Chemistry: Photoswitch in RNA Activity Control and Development of Photoredox Catalysis
Get PDFThis dissertation is structured into two principal segments. The initial segment elucidates a series of synthetic works involving artificial molecules, specifically featuring the photosensitive azobenzene. These molecules facilitate remote control over the structure and functionality of biomolecules, with subsequent applications in regulating biological processes. The latter segment concentrates on the design and enhancement of organic photocatalysts, utilizing traditional acridine ions as a foundation. This section details the development of diverse organic photocatalyst-promoted processes, including photo Lewis acid catalysis, photo Brønsted acid catalysis, and photoredox reactions
Differences in Mental Health Outcomes in Immigrant vs. U.S.-Born Populations in Urban vs. Rural Areas in the United States
Get PDFBackground
The immigration process to the United States creates distinct mental stressors. These stressors are influenced by socioeconomic factors including income, education level and insurance status. In rural America, these factors are intensified due to a poor healthcare infrastructure that is limited. This study examines the relationship between urban-rural residence and mental health outcomes among immigrants vs. native-born residents in the United States.
Methods
Data from the National Health Interview Survey (NHIS) from 2019 and 2022 were used to examine the relationship. The exposure of interest was place of birth, and the outcome of interest was the presence of clinically significant mental health symptoms. Potential confounders were the ratio of family income to the federal poverty level, education level, region, sex, age, health insurance status, and race/ethnicity. Descriptive statistics were examined, and then bivariate analysis and an adjusted multiple logistic regression model were fitted to understand the relationship between exposure and outcome. Stratified analysis by urban-rural classification and poverty status was considered for effect measure modification.
Results
Based on the results, residents in nonmetropolitan areas reported the highest prevalence of clinically significant mental health symptoms (10.8%) compared to residents in large central metropolitan areas (8.6%). However, this trend was reversed in adjusted logistic regression models, with residents of non-metropolitan areas exhibiting significantly lower odds of clinically significant mental health symptoms (OR= 0.85, 95% CI = 0.75-0.97), compared to those living in large central metro areas. Furthermore, NHIS participants born outside the US had significantly lower odds of clinically significant depression or anxiety (OR = 0.41, 95% CI = 0.36-0.48) compared to U.S.-born residents. These findings highlight mental health disparities by geographic residence and nativity status and highlight the need for further research to better understand mental health disparities based on duration of residence in the U.S. and within certain geographic regions of the country
Conclusion
This study found that poverty and lower education level were associated with higher levels of clinically significant mental health symptoms; these relations were stronger among U.S.-born adults. Foreign-born adults in the United States had lower odds of reporting clinically significant mental health symptoms compared to U.S.-born individuals after adjusting for socioeconomic and geographic factors. These findings highlight the need for mental health interventions that address socioeconomic-related stressors among U.S.-born populations while ensuring culturally responsive approaches to treat the unique stressors of the immigration process. Future studies should examine how the length of U.S. residence affects mental health outcomes and explore regional differences, particularly in the southern U.S
Naloxone Availability and Affordability: An Analysis of Pharmacies across New York State
Get PDFThe United States (US) has experienced a significant increase in the number of opioid overdose deaths since 1999. Drug overdoses are now the leading cause of accidental death in the US, surpassing other injury causes such as motor vehicle accidents. Opioids are most commonly associated with drug overdose deaths. The opioid overdose reversal medication naloxone, commonly known by the brand name Narcan®, has gained popularity in recent years as a critical tool for reducing the number of opioid overdose deaths. Naloxone Access Laws (NALs) and standing orders have been implemented by states nationwide in an effort to increase the availability and distribution of naloxone. In this three-paper dissertation, I examine the availability and affordability of naloxone in pharmacies since the New York State (NYS) NAL and standing order were signed into law. My research revolves around the central question: Is naloxone accessible in NYS pharmacies? In answering this question, I can determine whether the NYS NAL and standing order are being effectively implemented and whether they are meeting their intended goal to increase the availability of naloxone for consumers in the pharmacy setting.
In paper 1, I developed a probability sample of pharmacies across the state and leveraged a secret shopper study design to collect data on whether naloxone was in stock, available without a prescription, and the out-of-pocket cost. Findings from paper 1 show variation in naloxone access across the state and high out-of-pocket costs for consumers. In paper 2, I expand on the knowledge developed in paper 1 by determining the influencing factors of naloxone availability and cost variation across the state. Findings from paper 2 suggest that pharmacy type is the greatest predictor of availability, and that demographic characteristics and rurality do not influence naloxone availability and cost. In paper 3, I aim to provide the necessary contextual information around naloxone dispensing by conducting semi-structured interviews with currently licensed and practicing NYS pharmacists. Findings from paper 3 show there are several barriers and facilitators to naloxone dispensing from the perspective of pharmacists. In addition to the barriers and facilitators to dispensing, findings from paper 3 illuminated both the pervasiveness of stigma as well as the disconnect between perceived importance and practicality. Nearly all participants independently discussed the stigma related to naloxone. Additionally, participants reported that they believed pharmacies were a critical access point and important for increasing naloxone availability in the community, something commonly posited in the literature. Despite that, participants reported that customers infrequently asked about or purchased naloxone. The disconnect between the perceived importance of pharmacy availability and the practical frequency of consumer purchases forces us to re-examine the idea that pharmacies are an effective location for dispensing naloxone, due in part to customer awareness, comfort, and cost.
This three-paper dissertation contributes key findings to the existing literature. Findings from paper 1 suggest that while cost barriers remain, naloxone in the pharmacy is widely, yet unevenly, available across the state. Despite variation, rates of availability are high compared to findings from other states. Findings from paper 2 suggest that the variation in naloxone availability is not likely due to regional or demographic attributes such as rurality, race, ethnicity, and age, but instead due to the type of pharmacy, with chains being more likely to have naloxone available. Furthermore, naloxone cost is not influenced by pharmacy type, region, or other demographic or economic attributes. Findings from paper 3 suggest that the NYS NAL and standing order have been effective in increasing naloxone access in pharmacies and that pharmacists are accurately carrying out the policies as intended. This is supported by the findings in papers 1 and 2 as well. However, findings from paper 3 call into question whether the effort to increase naloxone in the pharmacy setting is resulting in the population at the highest risk of overdose having increased access to naloxone. Furthermore, findings from paper 3 suggest that we need greater exploration into understanding the impact of stigma on the design and implementation of NALs and standing orders
The Influence of Complex Terrain on the Turin, New York Tornado of 2023
Get PDFAlthough uncommon as compared to other regions of the United States, the Northeast does experience significant tornados; those rated F/EF3 and above, of which some have had profound impacts on the region. Due to the diverse topography of the region, including its many northsouth oriented river valleys, most of these significant tornados traversed considerable changes in elevation throughout their lifetime. This study seeks to better understand the impacts of local topography on the intensity and overall progression of a significant tornadic event through using the most recent Northeast EF3: the Turin, NY tornado. With the consideration of previous studies involving the effects of terrain on tornados, we broke terrains effects into two factors: valley channeling, where a valley favorably oriented can forced a backed surface flow and increase low-level shear, producing an environment better capable of severe hazards in said valley, as well as vortex stretching, where descent/ascent of terrain such as off a hill causes stretching and spin up of the vortex or vice versa. A synoptic and mesoscale overview of the event was carried out first, finding a low-end tornadic environment. Model simulations of the Turin supercell were carried out using the Weather and Research Forecasting (WRF) model to test the effects of various terrain configurations on the strength and progression of the storm, providing an in-depth analysis of both the valley channeling and vortex stretching effects previously mentioned. It was found the combination of both effects was responsible for the significant intensity of the Turin tornado, as the storm was noticeably weaker in the absence of these effects. Additionally, it was found these effects play a secondary role to storm-scale effects such as storm splitting, mergers, and nudges in alteration of the mesocyclonic vortex. Links were drawn to other noteworthy past events, providing confidence in our findings. Keywords: Significant tornado, effects of topography, Northeast US tornad
Coaggregation with Actinomyces Naeslundii Reduces Corynebacterium Matruchotii Cell Division Rate and Increases in Cell Length
Get PDFCorynebacterium matruchotii is believed to form a scaffold-like structure within the human oral cavity so that other species of bacteria have a place to bind. Many types of bacteria may be found within oral biofilms, commonly referred to as dental plaque. Actinomyces naeslundii are associated with dental caries and they are frequently found in dental plaques. Previous studies in our lab have demonstrated that A. naeslundii has a greater coaggregation rate with C. matruchotii than other Actinomyces species. The purpose of this study is to determine the effect of coaggregation with A. naeslundii on C. matruchotii growth kinetics. In this study, A. naeslundii grew in liquid cultures and the growth curves were measured. C. matruchotii was grown in the presence of heat killed A. naeslundii cells to determine the impact coaggregation has on cell growth. Additionally, plate counting was conducted at four time points. When grown with A. naeslundii cells C. matruchotii exhibited a reduction in cell growth and the C. matruchotii cells grew longer. Interactions between these species of bacteria may have implications for the role of the oral microbiome in the transition from oral health to disease
Contactin2(Cntn2)CreERT2 Mouse Line, A New Genetic Tool for Temporal Control to Trace the Developing Neurons in the Nose
Get PDFNeuronal migration is a vital process in embryonic development. In rodents, the very first neurons that originate from the olfactory placode migrate toward the developing brain as part of the migratory mass. This migratory mass includes Gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, and olfactory ensheathing cells—a type of glial cell.
Contactin-2 (Cntn2), also referred to as transiently expressed axonal surface glycoprotein-1 (TAG-1), belongs to the contactin family of proteins, which is part of the immunoglobulin superfamily of cell adhesion molecules. Cntn2 has been extensively utilized as a transient/stage-specific molecular marker for various neuronal populations, including commissural neurons of the spinal cord and motor neurons, sensory neurons emerging from the dorsal root ganglia as well as one of the few markers for TN neurons.
Currently, only a limited number of molecular markers are available to reliably label, trace, and manipulate early migratory neurons originating from the olfactory region. We recently reported Cntn2 expression in the TN via single-cell RNA sequencing of the developing olfactory system, pointing to the gene\u27s significance as a suitable molecular marker or genetic entry point for investigating early neuronal migration in the nasal area.
Based on this, we designed an inducible Cntn2CreERT2 knock-in mouse line. This study characterizes the new mouse line and describes how this model can serve as a valuable tool for time-controlled conditional manipulation of developing neurons. This mouse provides faithful Cre-mediated recombination in the spinal cord, sensory neurons, and migratory neurons of the developing nose.
Using Cntn2 tracing, we found that despite being regarded as a terminal nerve marker, Cntn2 is expressed by both TN and GnRH-1 neurons. This provides important insights for developmental studies focused on investigating GnRH-1 neuronal migration
Missing Information: A Content Analysis of U.S. Missing Persons Alerts Using the Missing and Endangered Persons Message Framework
Get PDFMissing and endangered person (MEP) alerts are a prominent messaging strategy used by law enforcement agencies in the United States to recover missing persons, with over 1,800 AMBER Alerts issued via the Wireless Emergency Alert (WEA) system and nearly 40 similar alerts introduced by state legislatures for other groups of missing people. Despite their prevalent use, the contents of MEP alerts have not yet been empirically examined. Drawing from warning message design and AMBER Alert best practices, we propose a new MEP Message Framework and use it to evaluate the contents of 4,053 MEP WEAs sent from 2013 to 2023. We find that the majority of messages are incomplete and lack detail about who is missing and how message receivers should respond, and often use jargon alert names (e.g. ‘AMBER Alert’) in place of specific details of the event. We conclude with proposed areas for future empirical and practical applications of the MEP Message Framework