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Identifying Splice Variant-Specific Functions of Casein Kinase 1α
No full textCasein kinase 1α (CK1α) is a serine/threonine protein kinase that acts in various cellular processes affecting cell division and signal transduction. CK1α is present as multiple splice variants that are distinguished by the presence or absence of a long insert (L-insert) and a short carboxyl-terminal insert (S-insert). When overexpressed, zebrafish CK1α splice variants exhibit different biological properties, such as subcellular localization and catalytic activity. However, whether endogenous CK1α alternatively spliced gene products also differ in their biological functions has yet to be elucidated. Here, we identify a panel of splice variant specific CK1α antibodies and use them to show that four CK1α splice variants are expressed in mammals. We subsequently show that the relative abundance of CK1α splice variants varies across distinct mouse tissues and between various cancer cell lines. Furthermore, we identify pathways whose expression is noticeably altered in cell lines enriched with select splice variants of CK1α. Finally, we show that the S-insert of CK1α promotes the growth of HCT 116 cells, as cells engineered to lack the S-insert display decreased cell growth. Together, we provide tools and methods to identify individual CK1α splice variants, which we use to begin to uncover the differential biological properties driven by specific splice variants of mammalian CK1α.</p
“Lost in Transcription?”: A Critical Performance Edition of Selections from "Pièces de Viole" by Marin Marais Transcribed for Violoncello and Basso Continuo
No full textMarin Marais (1656 –1728) was a French composer and viol virtuoso who wrote five books of Suites with close to 600 movements for one viol or several viols and basso continuo. In addition to its use as a melodic instrument, the viol was the primary continuo instrument used in Marais’ music and because its range is quite close to the cello’s, the modern instrument is a good candidate for transcriptions of Marais’ suites.The goal of this doctoral essay is to outline the process of making a critical performance edition of selections of Marais’ "Pièces de Viole." Performance practices of the French Baroque style and Marais’ unique use of ornamentation were examined in detail and the end result is an edition that is accessible to all cellists. This is especially important since transcriptions of Marais’ music are scarce and the primary sources that inform the performance practice of his music are not readily available. Marais was an innovator of the Baroque dance suite and of virtuosic writing for bowed string instruments, making access to his music important for expanding soloistic Baroque cello repertoire.The transcription process used here was modeled on Johann Sebastian Bach, who was a prolific transcriber of his own music, and will entail an analysis of his transcriptions to inform crucial transcription decisions for this edition. In addition, a realization of the basso continuo part for keyboard is provided as a convenience. This doctoral project is the first step of a lifelong project for the author of transcribing all five books of Marais’ Suite
“Bolivarian Authoritarianism”: Regime Change in Venezuela Under Hugo Chávez
No full textIn 1992, Hugo Chávez led an unsuccessful coup against the Venezuelan government and gained popularity by vowing to radicalize its democracy, eradicate political corruption and bring forth social equity. Chávez won over half of the votes in the 1998 national election. Once in office, he implemented systematic changes to the country’s political machinery that undermined important pillars of democracy and strengthened the absolute power of his presidency. Many controversies surround the Chávez regime and critics argue that it represented a new form of authoritarianism that combined elements of populism, nationalism, and political hierarchy. The objective of this dissertation was to seek answers for these thorny puzzles by systematically assessing Venezuela’s government under Hugo Chávez (1999–2013) to address two research questions. First, did Venezuela experience a turn from democracy to autocracy under Chávez? Also, what were the conditions that allowed Chávez to successfully capture and sustain power? By examining the political institutions, the economic structures, the social relationships, and the role of charismatic leadership during the Chávez regime, this dissertation includes an attempt to place his form of government precisely on the spectrum between the prototypes of democracy and authoritarianism.</p
Substantia nigra pars reticulata involvement in auditory hallucinations of treatment-resistant schizophrenia: a deep brain stimulation case report
No full textOne-third of schizophrenia patients exhibit treatment resistance, underscoring the need for mechanism-based interventions. We report that deep brain stimulation of the substantia nigra pars reticulata has acutely alleviated persistent auditory hallucinations by 64% in a treatment-resistant schizophrenia patient. Deep brain stimulation normalized hallucination-correlated elevation of intraoperative electrocortical theta-gamma phase-amplitude coupling at language-related cortical areas. These findings suggest aberrant cortical synchronization may be involved in the generation of verbal hallucinations and highlight subcortical modulation as a potential therapeutic strategy
Asynchronous Online Focus Groups: An Effective Approach to Engage Young Adult Women in Discussions on Mental Health Problems
No full textAs society becomes increasingly digital, qualitative research methods must continue to adapt and evolve to remain relevant and effective. This study aimed to evaluate the feasibility and utility of asynchronous online focus groups (AOFGs) as a platform to engage young women in discussions about mental health. The Learning Insights from Girls for Health (LIGHT) study utilized an AOFG to assess mental health problems and potential solutions among 52 young women, 18-25 years old, across the United States. This study analyzed survey data and transcripts from the LIGHT study to assess participants' perceptions and satisfaction with the AOFG approach, and to characterize participant engagement and interaction within the AOFGs. Over half (59.6%) of participants were "Extremely satisfied" with the approach, and 34.6% were "Somewhat satisfied." Participants highlighted Confidentiality, Flexibility, Connection and perspective sharing, and Equitable participation as strengths of the approach, and Lack of nonverbal and paraverbal cues, Disjointedness, and Prone to user and technical error as limitations. Two themes generated to characterize participant engagement and interactions in the AOFGs included (1) Engagement through storytelling elevates insights around mental health experiences and (2) Participant interactions included offering support in the form of advice, validation, and empathy. Results of this study indicate that AOFGs are a valuable platform for facilitating discussions about mental health in young women and are a practical and flexible approach to conducting qualitative research.</p
Tailored 6FCDA Copolyimides for Microporosity-Controlled CMS Membranes in C3H6/C3H8 Separation
No full textA series of 6FCDA-based fluorinated copolyimides (FCPs) were synthesized via controlled polycondensation by combining rigid aromatic diamines and fluorinated, ether-bridged dianhydrides to tailor the polymer backbone for enhanced gas separation performance. The structure–property design strategy involved the copolymerization of 2,2′-dimethylbenzidine, 1,4-bis(3,4-dicarboxyphenoxy)benzene dianhydride and a mixture of 2,4,6-trimethyl-1,3-phenylenediamine and 4,4′-oxidianiline. This combination was employed to disrupt polymer chain packing, increase the fractional free volume (FFV), and improve solubility in polar aprotic solvents, thereby facilitating polymer processing and membrane fabrication. Additionally, the resulting copolyimides exhibited excellent thermal stability, making them suitable candidates for further pyrolysis to produce carbon molecular sieve membranes (CMSs). Single-gas permeation measurements for propylene (C3H6) and propane (C3H8) at 35 °C revealed dual-mode sorption behavior and pressure-dependent transport characteristics. Among the synthesized polymers, the polymer with a DAM/ODA molar ratio of 3:1 (FCP-31) exhibited a C3H6 permeability of 271 Barrer and an ideal C3H6/C3H8 selectivity of 3 at 35 °C and 1 bar under pure-gas conditions. After 60 days of physical aging at 25 °C under dry N2, the C3H6 permeability decreased to 199 Barrer, whilel selectivity increased to about 4 at 1 bar. Carbonization of the FCPs produced CMS membranes with significantly enhanced selectivity. Fresh CMS membranes demonstrated a C3H6 permeability of 8 Barrer and an ideal C3H6/C3H8 selectivity of 16 at 1 bar. However, both permeability and selectivity decreased with increasing feed pressure up to 6 bar. After 60 days of ambient storage, the CMS membranes showed a reduced C3H6 permeability of 5 Barrer and an increased selectivity of 19, indicative of physical aging effects. These findings highlight the critical influence of the monomer structure on the design of 6FCDA-based fluorinated copolyimides and their derived CMS membranes, demonstrating their potential for efficient C3H6/C3H8 separation
Quantification of sulfur compound emissions from Sargassum Strandings
No full textMassive strandings of pelagic Sargassum release large quantities of hydrogen sulfide (HS), sulfur dioxide (SO), and dimethyl sulfide (DMS), posing risks to human health and local air quality. Emission factors needed to model and mitigate impacts are currently lacking. This study quantified sulfur emission factors from decomposing sargassum under laboratory conditions. Sargassum and seawater were collected from Key Biscayne, Florida, during summer and winter to investigate seasonal variability and the influence of seawater. Decomposition was monitored in sealed chambers over 14 days, measuring daily total sulfur, HS, and SOusing a UV fluorescence analyzer. DMS was analyzed by gas chromatography-mass spectroscopy (GC-MS). Sulfur emissions peaked within two days of decomposition before gradually declining. Seasonal variation was observed in emission rates, with summer samples exhibiting higher emission rates (average total sulfur peak: 3440 μg/kg-day in summer samples) compared to winter samples (71.2 μg/kg-day). The presence of seawater enhanced sulfur emissions across seasons. The highest total sulfur emission factor was observed in the "summer with seawater" condition, peaking at approximately 5190 μg/kg-day. HS was the dominant sulfur species (29% on average). DMS was the major volatile organic compounds. These findings demonstrate that seasonal factors and environmental conditions are key determinants of sargassum sulfur emissions. The quantified emission factors can inform public health management strategies, highlighting the need for rapid removal of water-saturated sargassum, particularly during summer, to mitigate HS release. The detection of DMS and SOindicates that sargassum strandings are a significant coastal source of aerosol precursors, impacting atmospheric chemistry
Predicting Atlantic Bonefish (Albula vulpes) Fork Length From Head Morphometry
No full textThis study developed predictive models using generalized linear statistical analyses to estimate Atlantic bonefish (Albula vulpes) fork length (FL) dependent on four head morphometry covariates: snout length, eye diameter, postorbital head length, and head length. A total of 257 South Florida bonefish were examined, which ranged from 28 to 720 mm FL. Each of the morphometric measurements was highly correlated with FL, with coefficients of determination (r2) that ranged from 0.9592 for eye diameter to 0.9959 for head length. Total length (TL) was also highly correlated with FL. Sex differences in the morphometric measurements were examined; however, no significant sexual dimorphism was detected. All of the morphometric measurements examined were good predictors of Atlantic bonefish FL and TL
MRI-Based Delta Necrosis as a Prognostic Marker Following Neoadjuvant Chemotherapy in Soft Tissue Sarcoma
No full textBackground: The prognostic value of treatment-induced necrosis in soft STS remains uncertain. This study evaluated whether MRI-based changes in necrosis (Δ necrosis) between pre- and post-neoadjuvant chemotherapy scans correlate with pathologic necrosis and clinical outcomes. Methods: In this retrospective cohort, 27 patients with STS who received neoadjuvant chemotherapy and underwent pre- and post-treatment MRI were analyzed. Necrosis was graded categorically (95%), and Δ necrosis was calculated as the change in estimated necrosis between scans. Correlations between MRI-derived and pathologic necrosis were assessed using Spearman’s rank coefficient. Survival analyses (progression-free, local recurrence-free, and disease-specific overall survival) were performed using Kaplan–Meier and log-rank tests. Results: Post-treatment MRI necrosis moderately correlated with pathologic necrosis (ρ = 0.44, p = 0.028), whereas Δ necrosis showed a weaker, nonsignificant correlation (ρ = 0.24, p = 0.24). Neither MRI-based nor pathologic necrosis thresholds were associated with survival outcomes. Conclusions: MRI-based Δ necrosis did not predict pathologic necrosis or oncologic outcomes in STS, suggesting that radiologic changes in necrosis may not serve as reliable markers of therapeutic response. Future studies integrating quantitative imaging and standardized pathology protocols together with future exploration of molecular tools such as ctDNA are needed to refine treatment assessment in STS
