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    71446 research outputs found

    Mosaic nucleic acids that bind purine nucleotides

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    Models for the origin of life have maintained that the first cells relied upon a single biopolymer for both genotype and phenotype. RNA may have provided these activities through its ability to transfer information via base-pairing and its ability to fold into functional structures. It follows that a comprehensive account of abiogenesis would include an understanding of prebiotic ribonucleotide synthesis. However, studies along these lines have shown that, depending on conditions, prebiotic chemistry may yield diverse nucleotides; some of which are based on sugars other than ribose. This monomer pool would likely support the polymerization of nucleic acid molecules characterized by a heterogeneous sugar-phosphate backbone. Copies of such mosaic nucleic acid (MNA) would conserve sequence information, but not the order and content of sugars in the sugar-phosphate backbone. Might MNA represent a possible source of early biological activity? The answer to this question largely depends on whether the structural heterogeneity of the sugar-phosphate backbone would allow for the emergence of selectable function. To test this possibility, we used in vitro selection to isolate purine nucleotide-binding MNA aptamers from a large library of random MNA sequences (containing an ∼1:1 mixed assignment of deoxy- and ribonucleotides). We report two MNA aptamers that bind either ATP or GTP with weak affinity (apparent KDs = ∼350 µM each) and moderate to high specificity. We conclude that variations in nucleic acid backbone content, perhaps introduced by imprecise synthesis, may not have posed an insurmountable barrier for the emergence of simple biological function.Medical SciencesMedical Science

    Autistic Play: Examining Theatrical Approaches to Building Self-Esteem & Practical Life Skills for Individuals with Autism Spectrum Disorder

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    This research explores the intersection of autism spectrum disorder (ASD) and performing arts, focusing on how theatrical participation enhances self-esteem, social skills, and practical life competencies in autistic individuals from the autistic person’s perspective. By centering the voices of autistic performers, this work challenges traditional narratives dominated by non-disabled voices and highlights the critical need for authentic representation in the arts. Through a combination of case studies, personal testimonials, and an analysis of historical and modern theatrical practices, this research reveals the transformative impact of performance on autistic individuals. Metrics such as professional development (Metric I), personal growth (Metric II), and social gains (Metric III) frame the analysis, demonstrating how participation fosters inclusivity and breaks down societal barriers. This study advocates for universal design and inclusion within arts organizations to create equitable opportunities for all. The conclusions of this study help highlight the importance of elevating autistic voices in research and practice, contributing to more inclusive frameworks in both the arts and broader societal contexts

    Improving Second-Grade Reading Comprehension Through a Sustained Content Literacy Intervention: A Mixed-Methods Study Examining the Mediating Role of Domain-Specific Vocabulary

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    This mixed-methods study explores the relationship between early elementary students’ domainspecific vocabulary knowledge and their ability to comprehend grade-level reading passages on unfamiliar science topics. Specifically, this study used (a) structural equation modeling (SEM) to examine the extent to which students’ networks of domain-specific vocabulary knowledge in Grades 1 and 2 mediated the effects of a Tier 1 content-based literacy intervention on domainspecific reading comprehension scores in Grade 2 (N = 2,156); and (b) quantitative survey and qualitative interview data from teachers (N = 48) to surface new themes about teacher vocabulary instruction that might suggest potential explanations for the SEM findings. SEM analysis revealed that students’ domain-specific vocabulary knowledge in first and second grade explained 69% of the treatment effect on a domain-specific reading comprehension outcome. Results from the quantitative survey also indicated that treatment group teachers reported providing more incidental exposures to vocabulary than control teachers (Effect Size [ES] = .54) and qualitative analyses revealed that teachers with high incidental exposures tended to provide expanded opportunities for their students to engage with words and to connect words to topics. Findings from this mixed-method study paint a more complete picture of (a) the important role domain-specific vocabulary knowledge plays in facilitating reading comprehension transfer in the domain of science, and (b) what teachers do during vocabulary instruction to promote transfer in domain-specific reading comprehension.Accepted Manuscrip

    CTCF/RAD21 organize the ground state of chromatin-nuclear speckle association

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    The interchromatin space in the cell nucleus contains various membrane-less nuclear bodies. Recent findings indicate that nuclear speckles, comprising a distinct nuclear body, exhibit interactions with certain chromatin regions in a ground state. Key questions are how this ground state of chromatin-nuclear speckle association is established and what are the gene regulatory roles of this layer of nuclear organization. We report here that chromatin structural factors CTCF and cohesin are required for full ground state association between DNA and nuclear speckles. Disruption of ground state chromatin-speckle contacts via either CTCF depletion or cohesin depletion had minor effects on basal level expression of speckle-associated genes, however we show strong negative effects on stimulus-dependent induction of speckle-associated genes. We identified a putative speckle targeting motif (STM) within cohesin subunit RAD21 and demonstrated that the STM is required for chromatin-nuclear speckle association, disruption of which led to impaired induction of speckle-associated genes. In contrast to reduction of CTCF or RAD21, depletion of the cohesin releasing factor WAPL stabilized cohesin on chromatin and DNA-speckle contacts, resulting in enhanced inducibility of speckle-associated genes. In addition, we observed disruption of chromatin-nuclear speckle association in patient derived cells with Cornelia de Lange syndrome (CdLS), a congenital neurodevelopmental diagnosis involving defective cohesin pathways, thus revealing nuclear speckles as an avenue for therapeutic inquiry. In summary, our findings reveal a mechanism to establish the ground organizational state of chromatin-speckle association, to promote gene inducibility, and with relevance to human disease.Chemistry and Chemical BiologyAuthor's Origina

    “It’s Eat or Be Eaten,” An Exploration of Cannibalism in Modern Japanese Manga

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    Over the past two decades, Japanese manga has become a worldwide sensation. In that same timeframe, the medium has seen a surprising increase in depictions of cannibalism. What is most surprising, however, is that the protagonists are the cannibals, not the villains. This paper sets out to answer why Japan is producing so much art featuring cannibalism, when and why this trend began, why it is so prevalent in the medium of manga, specifically, and finally, why cannibalism is most often included as a method of increasing power. As there is no previous scholarly analysis of this trend, this analysis is largely grounded in the history and culture of Japan, its art, and its post-war social and economic situation. By tracking the development of manga this paper reads the medium itself as being created through the process of cultural anthropophagy, with its latent cannibalistic tendencies becoming more explicit following economic trouble. First with the bursting of the bubble economy in the early 1990s and then with the global recession of 2008. The alienation created by these troubles caused a reactionary nationalism which has manifested in a reclamation of cannibalism as a method of decolonial resistance. That these economic crises have disproportionately affected men is reflected in the appearance of so many of these cannibal characters being in Shōnen manga [manga aimed at young men] specifically, which is itself a hotbed of cannibalistic competition

    The Quest for Educational Equity in Mexico

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    Abstract I examine the dynamics of implementing at-scale reforms to provide meaningful educational opportunities to disadvantaged students in Mexico. To effectively reduce social inequality and exclusion, education policies need a mix of system-wide and targeted efforts that are implemented at scale and sustained long enough to become institutionalized. The resiliency of those policies requires an elusive balance between system-wide and targeted efforts, alignment between federal and state initiatives, and supportive politics. However, the politics of implementing system-wide reforms are more contentious than those involving targeted efforts because they disrupt entrenched interests, making such efforts harder to sustain. Targeted policies, while easier to implement, reinforce the segregation of students into different educational tracks of varying quality

    The Care of Foreigners: A Brief History

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    Author's Origina

    Rumi and the Seven Cities of Love: The Path from a Divided Society to an Ever-advancing Civilization

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    The poet Rumi became transformed when he met the mystic Shams. The seven stages of the transformation are present in various works of the great mystical poets and mystical religious tracts. This work uses these seven stages, sometimes called seven valleys, sometimes seven cities, and attempts to build the unrecorded dialog that may have taken place between Rumi and Shams. The written works of Rumi as well as the memoir attributed to Shams are also used to form their potential dialogue in their own words when possible. Historical information is used as landmarks to guide the narrative. The poems presented from Rumi are original translations rendered into English from the Persian. The concept that resonates through the works of Rumi is perhaps the idea of love as a fire that purifies as a force of transformative action. The second section of this work similarly follows the seven stages used in the Rumi narrative but for an objective presentation that applies much of what Rumi and Shams share as applied to today’s challenges as a non-fiction narrative based on recent research referencing relevant works. Ideas such as empathy extend from the Rumi narrative into this section. Here, the scientific method is used when applicable. Mathematical principles including those used in the underpinnings of Artificial Intelligence (AI) and other areas of science such as Quantum Computing are used to help create an objective narrative. Effort is made to present findings while allowing the reader to decide the conclusions themselves. The final section includes a peer-reviewed paper, in Appendix A, that has been accepted for presentation and publication at the AI Large Language Model conference on November of 2024. This paper and subsequent completed work provide a framework to simulate and practically apply the concepts from sections one and two. The methods presented in these papers provide a means to run simulations of various types of group dynamics using Large Language Models and evaluate their efficacy in overcoming group polarization and finding solutions to extremely challenging problems

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