University at Albany, State University of New York
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An Analysis of Differential Object Marking in Copala Triqui
Get PDFIn this thesis, I review and investigate differential object marking in Copala Triqui, which uses the word man to overtly mark accusative case. Overt case marking is optional in some contexts and required in others. I describe the current literature on the topic and summarize the findings of other researchers on the optionality of man. Additionally, I examine another way to analyze differential object marking according to the qualities of the object only (“local”) or the relationship between the subject and object (“global”). The labels of local and global can be applied to existing analyses. The animacy, personhood, and pronominal status of subjects and objects have the biggest effect on the optionality of man. I identify nine types of subjects and objects according to those categories. These categories can be used to identify if there is existing data for each combination of subjects and objects. For those missing data points, I suggest example sentences to be used in elicitation. The optionality of man is a question of continuing research, and the findings of this paper can serve as a guide to future researchers about the outstanding questions and missing data points
Psychedelic Expectancies and Post-traumatic Stress Disorder Symptoms
Get PDFMillions of Americans struggle with posttraumatic stress disorder (PTSD) every year. Though typical treatments work for some, patients often drop out of treatment. Given that patients are often retelling their traumatic experiences, or confronting stimuli and situations that are relevant to the experience, psychotherapy for PTSD can be psychologically demanding and intensive. These factors provide a further understanding for the high rates of PTSD treatment attrition. Psychedelic assisted psychotherapy (PAP) is a potential option to mitigate these concerns. Preliminary research on PAP has revealed effective and promising results. However, questions about PAP and their public perception remain. Furthermore, treatment expectancies, or an individual’s expectation of treatment efficacy, may help inform treatment efforts. The current study examined expectancies related to psychedelic use and PTSD symptoms. A total of 434 individuals participated in the study and completed measures via an online survey. Paired sample t-tests revealed that several expectancy means differed significantly from each other, with expectancies for numbing receiving the highest score and reexperiencing receiving the lowest score. A zero-inflated negative binomial regression indicated that, in general, participants expected psychedelics to slightly worsen their overall symptoms. Additionally, participants experiencing greater PTSD symptoms reported more negative expectancies. However, results varied when looking at specific expectancy groups, with some findings indicating more positive expectancies. Overall, these findings offer various implications; however, the field needs more research to fully understand the facets that influence psychedelic use expectancies
Ribosome Hibernation Factor Induces Antibiotic Persisters of Mycobacterium Tuberculosis in Neutrophil-Rich Lung Lesions
Get PDFMycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) with ribosomal protein paralogues that lack this motif and do not bind to zinc (C-). The C- paralogues in mycobacteria are located within an operon regulated by the zinc uptake regulator, Zur. During zinc starvation, the mycobacterial protein Y, Mpy binds to the decoding center of the 30S subunit of the C- ribosome, stabilizing 70S inactive and hibernating monosomes. Mpy binding to the ribosome is facilitated by the zinc-binding and regulated protein, Mpy recruitment factor, Mrf. Mrf is co-transcribed with the C- proteins but, in its zinc-bound form, is recognized and degraded by the caseinolytic protease (Clp) system in growth-permissive zinc concentrations. In its zinc-free form, Mrf binds to the 30S subunit to help recruit Mpy to the ribosome. Because Mpy is constitutively expressed, we used Mrf to create a novel fluorescent reporter to visualize zinc-starved mycobacteria with physiological conditions promoting ribosome hibernation in vitro and in vivo. Using this surrogate reporter system, we demonstrated that the subpopulation of cells with Mpy-dependent ribosome hibernation contributed to ~50-60% of the overall mycobacterial population in vitro. Cells expressing the reporter exhibited Mpy-dependent metabolic slowdown and growth arrest.
Furthermore, we determined that Mpy-dependent ribosome hibernation contributes to nascent polypeptide translation attenuation and helps to prevent oxidative stress. In a high-burden, C3HeB/FeJ mouse model of chronic infection, we observed ~2-3% of the bacterial population expressing our fluorescent reporter. Upon treatment with isoniazid, the percentage of bacteria fluorescing increased from 2% to ~40% in an Mpy-dependent manner. Using both the Mtb susceptible mouse strain, C3HeB/FeJ, and the Mtb resistant mouse strain, C57BL/6, we demonstrated that extensive neutrophil infiltration likely causes zinc-limited extracellular niches for which these bacilli reside. Through transcriptomics, we identified the zinc importer, ZIP2, and the metal chelator, S100A8/A9, as likely contributing factors depleting zinc from the extracellular environment, creating zinc-starved Mtb with Mpy-dependent hibernating ribosomes. These findings contribute to developing a new paradigm in which a subpopulation of non-replicating persisters of Mtb emerges in vivo through zinc chelation by extensive neutrophil infiltration during high-burden chronic infections. Our studies provide a novel means to study these bacteria by utilizing a fluorescent reporter system and microscopic visualization
Understanding Local and Large-Scale Drivers of Rainfall Variability and Change Over the Hawaiian Islands Region
Get PDFHawaiian rainfall variability is strongly influenced by anthropogenic climate change and natural variability (e.g., Pacific Decadal Oscillation (PDO), Pacific North American (PNA) pattern, El Niño–Southern Oscillation (ENSO)). For local decision-makers and resource managers, understanding the drivers of rainfall variability and change in Hawai‘i is crucial for climate adaptation and mitigation planning. Previous studies have applied statistical and dynamical downscaling to produce high-resolution rainfall projections for the Hawaiian Islands region. However, to date, downscaling has only been used to investigate the influence of anthropogenic forcing on late-century rainfall projections for the Hawaiian Islands. For regions like Hawai’i, that are highly vulnerable to the effects of climate change and influenced by natural variability, there is a need for regional climate projections that investigate the influence of anthropogenic climate change in the presence of natural variability. A better understanding of the local and large-scale processes that drive rainfall variability and change in Hawai’i could help improve forecasts and climate projections and ultimately aid climate adaptation and mitigation planning across the State. Thus, this research addresses the following questions: 1) What is the role of natural variability in near-term rainfall projections over Hawai‘i? 2) What physical mechanisms drive the near-term rainfall changes over Hawai‘i? and 3) What is the relationship between the largescale circulation, natural climate variability, and wintertime Hawaiian rainfall disturbances?
First, the Weather Research and Forecasting (WRF) model was applied for dynamical downscaling to analyze near-term (2026–2035) rainfall projections over the Hawaiian Islands region. Of key interest is understanding the relative role of the anthropogenic forcing compared to natural variability in the near-term projections. Results indicate that increases in rainfall are iii expected across the islands, with the largest increases along the windward slopes of Big Island and Maui, during the wet season. In a future climate, it is also expected that the positive PDO phase will bring increases in rainfall to the windward slopes of Big Island and decreases or no change elsewhere. Overall, results suggest that natural variability will continue to mask anthropogenic climate change in the near-term future, making it difficult to detect a robust signal above the noise.
Second, to investigate the physical mechanisms that drive near-term rainfall changes in Hawai‘i, a moisture budget analysis was performed over the Hawaiian Islands region using both the downscaled WRF output and the driving global climate model (GCM) data. The moisture budget was decomposed into thermodynamic, dynamic, and eddy-driven components. Results indicate that the dynamic component dominates the near-term hydrological changes over the Hawaiian Islands region during both seasons, indicating that the near-term rainfall changes are driven primarily by changes in the mean circulation. Though less dominant, the thermodynamic component, i.e., changes in humidity accompanied by warming, plays an important role in the Hawaiian Islands moisture budget as well. It was also found that the transient-eddy component plays an important role in the wet season moisture budget, which can be attributed to increased synoptic activity during winter (i.e., Kona lows and cold fronts).
Third, to investigate the large-scale drivers of rainfall variability and change in Hawai‘i, the Self-Organizing Map (SOM) was applied to investigate the relationship between the large-scale circulation over the North Pacific, and its relationship to natural climate modes (e.g., PNA and ENSO) and wintertime rainfall disturbances in Hawai‘i (e.g., Kona lows, cold fronts). The SOM was trained with daily 250-hPa zonal wind anomalies from European Centre for Medium-Range Weather Forecasts reanalysis (ERA5). Results indicate that a zonally retracted jet is iv associated with the negative PNA/ENSO phase and above-normal rainfall across Hawai‘i, while a zonally extended jet is associated with the positive PNA/ENSO phase and below-normal rainfall across Hawai‘i. Further, to investigate future changes in the variability of the large-scale circulation, simulations from the Canadian Earth System Model version 5 (CanESM5) were projected onto the ERA5-trained SOM. Generally, results indicate that zonally retracted and poleward shifted jets are expected to become more frequent in a future climate (2071–2100). Overall, these results suggest that Hawai‘i will experience increased PNA/ENSO variability, increased frequencies in cold fronts and Kona lows, and decreases in wet season rainfall in a future climate. Further, these results highlight the usefulness of the SOM in bridging the gap between anthropogenic-induced changes in the large-scale circulation and local rainfall-producing weather types
Panel: Risk, Information, and Society: Decision-Making in EM & HS
No full textThis panel session will explore the role of information for decision-making in the context of emergency management and homeland security. As apart of this session, we explore the informational needs, preferences, and practices among key stakeholders in both the public and private sector, including citizens, governmental agencies, policymakers, public officials, non-governmental organizations, and the media. Expert panelists will be asked to consider numerous questions, including: how do these decision makers obtain information? How do they process and analyze that information? How do they use that information to make decisions during both ‘blue sky’ days and emergent events? What gaps exist between current policies, practices, and procedures and the evolving needs of different stakeholders, particularly in the context of historically underserved, underrepresented, and marginalized communities? Taken together, the panelists will explore these and other issues that occur at the very nexus of information, risk, and society
Exploring the Epitranscriptomic Response to Senolytics and Senomorphs in Cellular Models of Aging
Get PDFIn senescence that occurs with aging, cells stop dividing and initiate a pro-inflammatory program called the senescence associated secretory phenotype (SASP). SASP can lead to cell damage and has been linked to age-related conditions such as cancer, diabetes, osteoporosis, cardiovascular disease, Alzheimer’s disease, and osteoarthritis. The epitranscriptome regulates translation through post-transcriptional RNA modifications and can control when and how much of protein synthesis occurs. Several tRNA modifications that include 5-methoxycarbonylmethyl (mcm5U), 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), and mcm5Um (5-methoxycarbonylmethyl-2′-O-methyluridine) are linked to the translation of enzymes involved in the detoxification of reactive oxygen species (ROS), and defects in these tRNA modifications have been shown to promote senescence. We examined the reprogramming of tRNA modifications in response to pharmaceuticals that limit senescence or SASP in mouse embryonic fibroblast (MEF) cells and human lung fibroblast (IMR-90) cells. These cells were treated with senolytics (Navitoclax and Quercetin) and senomorphs (Metformin and Taurine). Small RNA was purified to analyze tRNA modifications by LC-MS/MS. We have demonstrated that senolytics and senomorphs can re-program tRNA modifications in wild type mouse embryonic fibroblasts, specifically 5-methylthio-2-methyluracil (s2mo5U), 7-methylguanosine (m7G), 5-methylcytosine-2-thiouridine (mcm5s2U), 2’-O-methylguanosine (Gm), N1-Methyladenosine (m1A), and 5-methoxyuridine (mo5U). We have also demonstrated that senolytics and senomorphs can re-program tRNA modifications in senescent human lung fibroblasts, specifically 7-methylguanosine (m7G), 1-methylguanosine (m1G), N2,N2-dimethylguanosine (m22G), 2-methylguanosine (m2G), 5-methylcytosine (m5C), N6-methyladenosine (m6Am), 5-methoxycarbonylmethyl (mcm5U), 2-thiocytidine (s2C), and pseudouridine (Ψ), with our studies being some of the first to explore this hypothesis. Our studies highlight the potential of using senolytic and senomorphic therapeutic agents to treat tRNA-related diseases
Molecular-Level Design of Heterometallic Precursors for Rechargeable Battery Cathode Materials
No full textThe synthetic methods for rechargeable battery cathodes are rapidly evolving along with the continuous advancement of the materials themselves. Utilizing precursors for the synthesis of Li- and Na-ion cathode materials are known to ensure a phase-pure product with isotropic element distribution, thereby further enhancing the electrochemical properties of the cathode material. As more cathode materials with complex compositions continue to emerge, the strategies for designing the corresponding precursors are also getting diversified. One of the most promising directions is the employment of single-source precursors (SSPs), defined as molecules that contain all necessary elements in the proper ratio and decomposable under mild conditions to yield phase-pure target compounds upon the low-temperature decomposition. This method both optimizes the synthetic pathways to existing materials and provides an access to new materials that are not accessible by conventional techniques.
In this dissertation, the advancement of multiple SSPs through appropriate methods with delicate design steps is described. In general, this work contributes to developing new preparation techniques for prospective Li- and Na-ion metal oxides for rechargeable batteries, as well as to applying the SSP approach to synthesize and characterize unknown materials. At the same time, this thesis provides a detailed analysis of the structure and properties of different SSPs and highlights some unusual cases of isomerism. The isomerization phenomenon not only alter the precursor design approach but also affects the thermal decomposition properties related to the synthesis of target materials
The Study of Ribosome-Amplified MetaBOlism, RAMBO, Effect In Vitro and in Live Cells
No full textQuinary interactions arise due to the extreme macromolecular crowding inside live cells. Quinary interactions affect intracellular protein stability, activity, and homeostasis. Ribosomes, traditionally known for their role in protein synthesis, have been found to engage in quinary interactions with metabolic enzymes, modulating their activity and thereby revealing a potential regulatory role for ribosomes in cellular metabolism. This phenomenon, termed the Ribosome-Amplified MetaBOlism (RAMBO) effect, was investigated in this dissertation through a series of in vitro and in vivo studies using primarily Nuclear Magnetic Resonance (NMR) spectroscopy.
Firstly, an NMR-based direct enzyme assay compatible with ribosome was developed and validated using pyruvate kinase (PYK) from Bacillus stearothermophilus as a probe. A high-quality Escherichia coli 70S ribosomes preparation was developed. Highly purified ribosomes were used to ensure that the observed amplification in enzyme activity was solely attributable to ribosomal interactions. Ribosomes were shown to significantly enhance the PYK activity and chemical cross-linking mass spectrometry (XL-MS) was used to identify key ribosomal binding sites of PYK, supporting the RAMBO effect.
Next, a general mechanism for the RAMBO effect was proposed and elucidated, where the ribosome external electric field (EEF)-substrate dipole interaction energy stabilizes transition states, significantly increasing the activity of triosephosphate isomerase (TPI) from Gallus gallus. NMR spectroscopy was performed to examine the quinary interaction surface of TPI binding to the ribosomes, and to access the TPI kinetic assay. XL-MS coupled with molecular docking were used to determine the potential TPI-ribosome binding conformations, providing structural models for the electric fields and substrate dipoles calculations. Ribosomal protein L11 was identified as the primary binding partner of TPI, confirming the origin of the RAMBO effect.
Finally, the in vivo RAMBO effect was studied in the context of glycolysis in E. coli using real-time pulse chase (RTPC)-NMR. The activity of pyruvate kinase I (PYFK) from E. coli was significantly enhanced in the presence of ribosomes, but this ribosome-mediated amplification was disrupted by the addition of ribosomal antibiotics in vitro. Kinetic flux profiling (KFP) further demonstrated the RAMBO effect observed in vitro also occurs in live cells, thereby confirming the role of ribosomes metabolic regulation and validating the RAMBO hypothesis
Intergenerational Ties, Sexual Orientation, And Health And Well-Being Of Sexual Minority Adult Children
Get PDFThe three studies in this doctoral dissertation explored overarching themes related to intergenerational relationships, health, and well-being of sexual minority adult children, using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health). The studies have shared but distinctive focal points, including various dimensions of intergenerational relationships, specific subsets of data sources, and methodologies. The first study used two latent growth curve models to examine how intergenerational relationships between adult children and their older parents evolve over time, specifically focusing on the emotional closeness gap between sexual minority and heterosexual adult children. The results showed that sexual minority status was significantly associated with lower emotional closeness to both mothers and fathers during early adulthood. The results also revealed that sexual minority status did not significantly impact the trajectory of maternal and paternal closeness from early to midlife. These findings suggest that sexual minority adult children have poorer intergenerational relationships compared to their heterosexual counterparts, and this disparity persists throughout adulthood without significant improvements over time. The second study investigated the impact of sexual minority status on parental financial assistance, focusing on general assistance and specific types of assistance (i.e., education, housing, and other expenses). The results revealed that, when considering overall financial assistance across all types, there was no significant difference based on sexual minority status; sexual minority adult children were not more or less likely to receive financial assistance compared to their heterosexual counterparts. However, when focusing on educational assistance, being a sexual minority seemed to confer an advantage, as parents were more inclined to provide financial support for the education of their sexual minority adult children. Therefore, the study found that the impact of sexual minority status on parental financial assistance may be type specific. The third study examined the mediating role of intergenerational relationships in the association between sexual orientation and two mental and physical health outcomes, depressive symptoms and self-rated health. The results affirmed the well-established link between sexual minority status and adverse mental and physical health outcomes, with a particularly robust association observed for mental health. Moreover, certain dimensions of intergenerational relationships, such as maternal and paternal closeness were identified as mediators in the relationship between sexual minority status and poor mental and physical health outcomes, although the patterns and relationships varied depending on the specific mediators. Taken together, these three studies present a complex story of how the intergenerational family context shapes the health and well-being of sexual minority individuals. Ultimately the findings highlight the importance of interventions and practices for sexual minority individuals and their families
Supporting At-Risk Kindergartners’ Subtraction Knowledge And Language Use Through Shared Book Reading.
Get PDFThe purpose of this study was to explore how shared book reading may promote meaningful, multimodal language interactions to support subtraction learning and language use and understanding for kindergarten students who have been previously identified as at-risk for mathematical difficulties. This study is underpinned by theoretical notions that language is developed in social contexts and is a multimodal phenomenon. In addition, this study is also shaped by sociocultural views of mathematics learning that position discourse at the core of mathematics learning. This study took a micro-ethnographic approach to qualitative research and utilized multimodal discourse analysis to analyze the data. The findings of this study illuminate the multimodal interactions that occurred during four shared reading sessions and present data that demonstrates how the students and their teacher utilized multiple modalities to jointly build knowledge about subtraction concepts and subtraction language. The three major findings demonstrate how: 1) the teacher used verbal and gestural scaffolding to help students learn and use subtraction language; 2) the students used multimodalities to identify potential moments of confusion and jointly build knowledge about subtraction concepts and language and; 3) the students demonstrated embodied cognition of subtraction concepts and language during shared reading through the use of gesturing. Upon interpreting the findings of this study and embedding them within the pre-existing research base, this study asserts how multimodal shared read alouds benefit at-risk kindergarteners’ understanding of subtraction concepts and language and support their mathematical language use