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WHAT IS DASH?
DASH is the central, open-access institutional repository of research by members of the Harvard community. Harvard Library Open Scholarship and Research Data Services (OSRDS) operates DASH to provide the broadest possible access to Harvard's scholarship. This repository hosts a wide range of Harvard-affiliated scholarly works, including pre- and post-refereed journal articles, conference proceedings, theses and dissertations, working papers, and reports.
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Recent Submissions
Characterization of Prefrontal ChAT-VIP Interneurons in Attentional Modulation via In Vivo Calcium Imaging and Chemogenetic Suppression
Attentional dysfunctions are prevalent and treatment-resistant cognitive deficits across numerous neuropsychiatric and neurodegenerative disorders. The medial prefrontal cortex is essential for top-down attentional control and is regulated by local inhibitory microcircuits and cholinergic modulation. However, the precise cellular mechanisms stabilizing prefrontal output during attentional demands remain poorly understood. To address this gap, we developed a novel operant behavioral battery to isolate three components of attentional control in mice: sensory engagement, sustained attention, and resistance to distraction. Our research focuses on choline acetyltransferase (ChAT) vasoactive intestinal peptide (VIP) interneurons, a rare subclass of cortical cells that uniquely co-release acetylcholine and GABA. Because these ChAT-VIP neurons provide temporally precise and developmentally tuned modulation, we hypothesize that they coordinate the excitatory-inhibitory balance in the medial prefrontal cortex to suppress maladaptive perseveration under high cognitive load. We combined our operant attention battery with in vivo calcium imaging and chemogenetic manipulation in ChAT-Cre mice. Preliminary findings indicate that chemogenetic silencing of ChAT-VIP interneurons unexpectedly improves overall accuracy and sensitivity, suggesting that tonically removing a predominantly GABAergic inhibitory brake enhances cue detection and attentional performance. Furthermore, calcium imaging revealed that prefrontal pyramidal neurons encode cue information and predict trial outcomes. By bridging population-level dynamics with cell-type-specific contributions, this research defines the regulatory role of local cholinergic drive in attentional control. Ultimately, uncovering these prefrontal microcircuit mechanisms may inform novel strategies for circuit-level interventions to restore cognitive function in disease.
Gut Microbiome Alterations in Parkinson’s Disease: A Metagenomic Analysis
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that has been increasingly linked to changes in the gut-brain axis and the composition of the gut microbiome. This thesis describes an independent computational reanalysis of a large publicly available shotgun metagenomic dataset of PD and control stool samples using a standardized diversity and differential abundance pipeline with explicit covariate adjustment and cross-validation across two independent statistical approaches. Key findings were subsequently tested for replication in a second independent PD cohort using a formal meta-analysis. We analyzed taxonomic and functional community profiles from 724 stool samples from 490 individuals with Parkinson’s Disease and 234 healthy controls. Low prevalence taxa and pathways were filtered out prior to analysis leaving 196 species level taxa and 397 pathways for downstream testing. We incorporated a second independent cohort of PD patients (Bedarf et al., 2017; 59 stool samples, 31 PD and 28 controls) using curatedMetagenomicData to test cross-cohort replication of results. Alpha diversity was largely overlapping among the groups. Beta diversity based on Bray-Curtis dissimilarity revealed high overlap between PD and control samples. Permutational multivariate analysis of variance (PERMANOVA) showed a significant association between disease status and community composition (R² = 0.0095, F = 6.91, p = 0.001) that remained significant after adjustment for age and sex. Differential abundance testing identified 62 of 196 species (31.6%) and 234 of 397 pathways (58.9%) to be significantly associated with PD at FDR 0.05, consistent with two recent multi- cohort meta-analyses of the PD gut microbiome (Romano et al., 2021; Nishiwaki et al., 2024). Meta-analysis of the 117 species with sufficient data in both cohorts identified 16 species as significant after FDR correction. The enrichment of Ruthenibacterium lactatiformans in PD was the strongest and most consistent finding (r = 0.25, FDR q = 5.5 × 10−10, I2 = 0%). Several taxa identified in the single-cohort analysis including Actinomyces oris and Bifidobacterium dentium did not replicate under this stricter cross- cohort test (I2 = 82% and 64% respectively). These results are evidence implicating the gut microbiome in PD pathogenesis. They demonstrate that a large proportion of individual microbial features can differ significantly between groups even when the effect size at the community level is small. This analysis provides a baseline to enable future extensions of this work including gut virome profiling and addition of further independent cohorts as they become available.
Democratic Commitment in Self-Determination Movements: A Comparative Study of Secessionist and Autonomist Organizations in Asia
This study examines whether secessionist and autonomist self-determination organizations differ in their commitment to democratic principles and practices. Although existing scholarship has extensively explored the causes, strategies, and legal dimensions of self-determination movements, comparatively little attention has been devoted to evaluating the democratic orientations of these organizations themselves. This study addresses that gap by systematically comparing the democratic commitments of secessionist and autonomist organizations. Democratic commitment is operationalized through five indicators derived from democratic theory and international human-rights norms: political pluralism, separation of religion and state, commitment to internationally recognized human rights, protection of minorities, and gender equality. The study analyzes 83 ethnic or regional self-determination organizations in Asia, including 38 secessionist and 45 autonomist groups operating in India, Pakistan, Myanmar, Malaysia, China, Iran, and Iraq. Organizations were evaluated on a 0-10 scale based on publicly available rhetoric and observable behavior, including manifestos, official statements, governance practices, peace agreements, and reports from international organizations and human-rights institutions. To improve comparability, the sample includes only countries or historically distinct regions containing both secessionist and autonomist organizations.
The findings reveal a substantial and statistically significant difference between the two groups. Autonomist organizations achieved a mean democratic score of 6.18, compared to 2.71 for secessionist organizations. The difference is highly significant (p 0.000001) and associated with a large effect size (Cohen’s d = 1.43). The study provides empirical support for the argument that autonomist organizations are, on average, more likely than secessionist organizations to demonstrate commitments to democratic principles. More broadly, the findings suggest that the mode through which self-determination is pursued may influence organizational behavior and their observable commitment to democratic principles, with implications for peace negotiations, autonomy arrangements, and post- conflict political development.
Open Access as Label and Rallying Cry: A Framework to Unify Two Senses of OA
Open access is both a label and a rallying cry. As a label, it minimally refers to the removal of price barriers from digital online scholarship. Often, though not always, permission barriers are also lowered or dropped. As a rallying cry, open access signals a commitment. The Budapest Open Access Initiative, for example, calls itself “a statement of principle, a statement of strategy, and a statement of commitment.” Similarly, the Bethesda Statement on Open Access Publishing and the Berlin Declaration on Open Access to Knowledge in the Sciences and Humanities have each made the case for open access as important, necessary, and enabling a public good. Just so with the newer Delhi Declaration on Open Access and São Paulo Statement on Open Access. Rights retention-style open access policies adopted by institutions worldwide can express commitments, too. Harvard’s policy, for instance, cites a commitment to “disseminating the fruits of its research and scholarship as widely as possible." My aim is to unify the label and the rallying cry under a single framework. In doing so, I draw on Bernard Suits’s analysis of gameplay in the philosophy of games. Although open access and its associated scholarly activities are decidedly not games, the way Suits defines ‘playing a game’ will be useful within our very different domain. Just as Suits’s definition consists of three elements, so too does the framework I propose. This three-element framework brings together the label and the rallying cry without conflating them; it demonstrates how the two senses of open access are related, while preserving their essential differences. Finally, the framework reminds us why fostering a commitment, or adopting the rallying cry, is so important: It’s not the case that open access would otherwise be too elusive or fleeting. On the contrary, the rallying cry matters precisely because the label is now so attainable, enduring, and embedded in scholarly practices. In other words, open access is ubiquitous and resilient, not rare and fragile, and a commitment keeps it in check. For the value of open access lies in the way we bring it about, not simply in our ability to apply a label to scholarship.
On the Free Indirect Speech of Very Minor Characters in Mrs. Dalloway
"Very minor" characters in Virginia Woolf's Mrs. Dalloway, who receive only a few sentences' attention before vanishing from the canvas of the novel, receive surprisingly consistent and intense depiction through free indirect speech, especially in the London street scene near the opening of the novel and the party scene near its close. Even in comparison with similar-looking scenes in Mrs. Dalloway's modernist cousin, Ulysses, Woolf's interest in narrating her very minor characters' inner lives stands out. Woolf's application of free indirect speech to individuals in large groups generates an effect related to, but different from, the more unified "social mind" Alan Palmer identifies in novelistic narration of communities, and Alex Woloch's account of very minor characters as foils, notable for their paucity of detail. Instead, Woolf emphasizes both the distance between those individual minds, and the preoccupations and misperceptions resulting in their neglect of vulnerable or marginal characters such as Septimus Smith and Ellie Henderson. Woolf found in the use of free indirect speech to depict large groups of very minor characters a peculiar narrative tool for depicting how the collective mind can lose track of those who enjoy no special status within it.