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Exploring EEG phenotype in a female fragile X syndrome mouse model
(2025-04-17) Ahmed, Asim; Cheng, Ning; Turner, Raymond; Bray, Signey Lauren
Background Fragile X Syndrome (FXS), the most common monogenic cause of autism, currently lacks effective, broadly applicable treatments. Despite promising preclinical results, many clinical trials have failed—highlighting the need for reliable translational biomarkers. Electroencephalography (EEG) has emerged as a promising tool, with recent studies identifying EEG abnormalities, particularly in male FXS patients and rodent models, such as increased gamma power and reduced or unchanged alpha power. However, female models remain understudied, despite FXS being an X-linked disorder with notable sex-based phenotypic differences. Additionally, few studies examine EEG biomarkers across developmental stages, though such comparisons are crucial for understanding disease progression. To address these gaps, we investigated EEG features in female fmr1 knockout (KO) mice—a well-established FXS model—at both juvenile and adult ages, comparing them to wild-type (WT) controls. Methods and Results EEG recordings were obtained using a wireless open-source EEG system (OSERR), with signals collected from frontal-parietal electrodes during three conditions: home cage, light/dark arena, and open field test. We analyzed absolute and relative EEG power, peak alpha frequency, theta-beta ratio, phase-amplitude and amplitude-amplitude coupling, and signal complexity. Our results showed that alpha, beta, gamma, and total absolute power were elevated in KO mice compared to WT at both ages. Gamma power (absolute and relative) increased with age in both genotypes, while relative theta power decreased in KO mice. Additionally, KO mice exhibited altered cross-frequency coupling, increased peak alpha frequency, and a reduced theta-beta ratio. EEG complexity, however, remained unchanged. Discussion and Conclusion Our findings reinforce gamma power elevation as a consistent EEG biomarker across FXS models, including female mice. However, not all biomarkers observed in FXS patients (e.g., peak alpha frequency, theta-beta ratio, and signal complexity) were mirrored in female KO mice, suggesting partial translational validity. Notably, differences between male and female fmr1KO mice also point to presence of a potential sex-specific EEG phenotypes. These results emphasize the need to consider sex and developmental stage when using EEG as a translational biomarker in FXS research and highlight which EEG features may be more reliably translated from animal models to human studies.
Identifying novel functions of the SHOX homeobox 2 gene within the developing mouse hindbrain
(2025-04-15) Hamilton, Gregory David; Cobb, John; Dyck, Richard; Shemanko, Carrie; Kurrasch, Deborah; Schuurmans, Carol
The SHOX homeobox 2 (Shox2) gene is required for proper embryonic development of the heart, limb, palate, spinal cord, and brain. The conditional inactivation of Shox2 in the developing central nervous system causes mutant mice to be born with impaired motor coordination and facial paresis, due to a loss of Shox2 expression in cerebellar Purkinje cells and facial visceral and branchial motor neurons. Neonatal lethality also occurs in these mutants 18-26 hours after birth due to an undescribed neural function of Shox2. Here, we characterized the spatiotemporal recombinase activity of the Hoxb1Cre, Egr2Cre, Atoh1-Cre, MafbCre, Hoxb4-ENE-Cre, Wnt1-Cre, and Nes-Cre mouse lines in the developing embryo, neonatal brain, and cochlea, before using a subset of these lines to conditionally inactivate (LOF) and overexpress (GOF) Shox2 in the developing mouse. Hoxb1Cre activity in rhombomere 4, from which facial visceral and branchial motor neurons arise, resulted in Shox2 GOF embryos with facial nerve fasciculation defects. Egr2Cre had activity in rhombomeres 3 and 5, which contribute cells to the ascending auditory pathway; generated Shox2 GOF mice subsequently showed significant reductions in both acoustic startle response and sensorimotor gating during pre-pulse inhibition tests. MafbCre was active in rhombomeres 5 and 6, and in brain interneuron populations; generated Shox2 LOF neonates died 14-24 hours after birth, following the detection of decreased inspiratory amplitudes, increased breath period variability, and greater apnea durations during whole-body plethysmography. Shox2 expression in these mutants was notably lost in the medullary medial reticular formation, which contributes to respiratory rhythm regulation in neonatal mice. This work provides evidence of novel roles for Shox2 in facial nerve fasciculation, acoustic startle modulation, and respiratory rhythm stabilization, and reinforces the necessity of iii Shox2 expression in the hindbrain for neonatal survival. These experiments also demonstrate the cellular and functional conservation between central pattern generators in the spinal cord and brainstem.
Curating DIY Community On Reddit A Feminist Subcultural Study of R/Cottagecore
(2025-04-16) Ramey, Hunter Caitlin; Keller, Jessalynn; Keller, Jessalynn; Shepherd, Tamara; Chan, Julia
Internet aesthetics are a form of style categorization that have prominent popularity within the social media use of girls and young women. Often aesthetics are interpreted as the mass commercialization of a style, sometimes inspired by previous subcultures like goth or punk. There is a bias within female youth cultural studies to pay significantly more attention to girls’ consumerist activities and less on the ways they interact, share and create using media. I investigate girls’ media production within cottagecore through the collection of 599 posts and 8151 comments made to the r/cottagecore subreddit between July 1st 2024 and August 31st 2024 to unearth the continuation of consumption-conscious subcultural activities such as do-it-yourself (DIY). I argue that close analysis can show meaning within these aesthetics beyond consumerism. Additionally, r/cottagecore negotiates space within an internet aesthetic which can be problematic as the colonial nature of the cottage and the aesthetic use of DIY (crochet, embroidery, cooking, sewing) has gained the attention of another internet phenomenon: the tradwife. However cottagecore can also be an aesthetic adopted by youth in rejection to overconsumption through progressive repurposing of traditionally feminine roles or by minoritized groups as a means of reclaiming a space. I analyze how r/cottagecore participants grapple with the complex environment of femininity, consumption and the intersectional considerations of participation.
Chemical Diversity in High-Mass Star-Forming Regions: A Comparison of Carbon-Chain and Complex Organic Molecules
(2025-04-14) Freeman, Pamela; Plume, René; Stil, Jeroen; Friesen, Rachel; Langill, Phil; Wieser, Michael
The dynamic evolution of star formation produces a diverse suite of molecules, whose emission reveals great detail about the physical and chemical conditions from which these species arise. In protostellar sources there are two categories of molecules distinguished for their diagnostic capabilities: complex organic molecules and carbon-chain molecules. Due to their different formation routes, these molecules distinguish a possible chemical dichotomy of protostellar regions. In this thesis, I study the large-scale structure and environment of high-mass protostellar regions through a systematic survey of complex organic molecules and carbon-chain molecules. I combine observations and modeling for a comprehensive view.
For the observations, I conducted a wide-band spectral survey with the Institut de ra-dioastronomie millim´etrique 30-m telescope and the 100-m Green Bank Telescope towards the three high-mass star-forming regions in the nearby molecular cloud complex Cygnus X: AFGL 2591, IRAS 20126+4104, and DR21(OH). I map these regions to gain spatial as well as spectral information about these sources. For the modeling, I use a newly built multi-component local thermodynamic equilibrium (LTE) model to determine the physical conditions of the gas environment these molecules arise from. The model identifies all molecular transitions for one or more species and simul-taneously fits these lines as defined by certain physical parameters – size, line width, columndensity, excitation temperature, and source velocity. In all three sources, I disentangle dif-ferent velocity and temperature components corresponding to known protostellar cores and outflows in the regions. In follow-up, I present results from a gas-grain code that determines the formation and destruction routes of these molecules. Both thermal and non-thermal mechanisms are needed to reproduce the abundances of the observed species. In this thesis, I also demonstrate the use of this python-based LTE model as a flexible and comprehensive way to analyze spectral line data cubes. Through a combination of wide-band mapping observations, LTE and non-LTE model analysis, and chemical modeling, I reveal the chemical and physical environments of protostellar regions.
Extending ModCP for Change Propagation Analysis in Multilingual Systems
(2025-04-09) Mirzaei Malekabad, Mohammadmoein; Walker, Robert James; Reardon, Joel; Maurer, Frank; Walker, Robert James
In software engineering, change propagation analysis is a technique that enables developers to identify and manage the ripple effects of software modifications. This process plays an important role in maintaining and evolving complex software systems, as the ripple effects of changes in such systems are often subtle and difficult to notice due to their size, complexity, and interdependencies. Without proper analysis, these hidden impacts can lead to unforeseen issues, such as functionality breakdowns and customer dissatisfaction. ModCP, an existing tool for change propagation analysis, excels in identifying the im-pact of changes within an environment that utilizes a single programming language. How-ever, modern software systems frequently integrate multiple languages for different purposes, which interact with each other, posing challenges that traditional change propagation tools are not equipped to address, particularly in managing cross-language change propagation. This thesis addresses this limitation of ModCP by extending its capabilities to support change propagation across multilingual systems. A general model for interactions among languages is proposed and two realizations of the proposed model are developed, specifi-cally for Java–TSQL and C#–TSQL interactions. These implementations enable ModCP to accurately trace and propagate changes across these language boundaries. The enhanced ModCP is evaluated through a number of examples from official sources and documentation to test its ability to handle inter-language change propagation, particularly in environments involving Java or C# and SQL. These examples compare the performance of the enhanced ModCP against the previous version of ModCP and an industrial tool, Find it EZ Dev Surge, using metrics such as precision, recall, and F1 score. The results demonstrate that the enhanced ModCP consistently outperforms its alternatives, achieving higher scores across all metrics by accurately identifying implicit dependencies and tracing inter-language data flows.
