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Chronic Illness Education 2025: Environmental and Psychosocial Interventions in Adolescent Depression
No full textAn Array of Facts : Anti-Lynching Literature and Bibliographic Control
No full textThis article argues that a tradition of anti-lynching literature uses documentary techniques to exercise bibliographic control over lynching discourse. That tradition, inaugurated by Ida B. Wells, offers an alternative to the lurid narrative accounts published in newspapers and the quantitative statistical accounts produced by academics. In that way, anti-lynching literature resolves a tension between qualitative and quantitative methodologies. While quantitative methods risk abstracting the lives lost to racial violence, qualitative methods risk reproducing the spectacle of violence in the process of describing it. That impasse has marked the archival turn in Black studies as a problematic of representation. How can the archival records used to enslave, imprison, and impoverish Black people also be used to write the history of Black lives? Reading anti-lynching literature as an achievement of bibliographic control shows how critical information practices index the scope of racial violence without contributing to its erasures. Building on the archival turn, this article suggests how other information technologies besides the archive contribute to historical memory in ways that attest to the durability of Black life
EVALUATING DNA-PKCS INHIBITION AS A THERAPEUTIC STRATEGY IN TP53-MUTANT GLIOBLASTOMA
No full textGlioblastoma (GBM) is the most aggressive primary malignant brain tumor in adults, characterized by marked heterogeneity, treatment resistance, and poor prognosis. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a key mediator of non-homologous end joining (NHEJ), the primary DNA double-strand break repair pathway in non-dividing cells. Its overactivity in GBM supports rapid repair of therapy-induced DNA damage, contributing to resistance against radiation and chemotherapy. This study investigated the therapeutic potential of DNA-PKcs inhibition in two patient-derived xenograft (PDX) models, HF3016 (newly diagnosed) and HF3177 (recurrent), originating from the same patient and both harboring TP53 mutations. Stable knockdown of PRKDC was achieved via shRNA, and its effects were evaluated in vivo using radiation, temozolomide (TMZ), or abemaciclib.
Knockdown alone did not improve survival, but in combination with radiation, DNA-PKcs suppression markedly sensitized tumors, particularly in HF3177-KD2, where deep and sustained knockdown was associated with durable, tumor-free survival in a subset of mice. In contrast, partial knockdown (HF3177-KD1) allowed post-radiation rebound of DNA-PKcs expression, limiting therapeutic benefit. HF3016 demonstrated additive effects of knockdown and radiation, with reductions in DNA-PKcs expression but no further suppression beyond baseline knockdown levels.
These findings highlight the importance of knockdown depth, context-specific responses, and the potential for selection of resistant clones when suppression is incomplete. DNA-Pkcs inhibition appears most effective as an adjunct to radiotherapy, but optimal benefit may require agents with robust brain penetrance and strategies to prevent compensatory repair pathway activation. This work supports further evaluation of DNA-PKcs as a therapeutic target in GBM and informs the design of biomarker-driven combination regimens
Poetic Playing Fields: The Israel Folktale Archives as a Social Arena
Get PDFThe literary biography of Yaakov Lasri, from his time as a frustrated transcriber of stories he heard from others until the publication of his last book, in which he molded stories with artistic freedom, is a voyage through the literary polysystem of Israel of his day and the literary and political fields available to him. His disappointment in the real and symbolic capital that the Israeli Folktale Archives (IFA) offered drove him to seek alternative literary fields at play within the political discourse that blossomed in the late 1960s. The Mizrachi discourse in which social-political marginality started to challenge the heart of the establishment also manifested itself as changes in the literary field, changes that allowed Lasri to receive generous financial support for the publication of his first two books from local institutions and organizations associated with Mizrachi Jews. These gave room to poetics and to genres that neither the scientific establishment (IFA) nor the literary establishment (written literature) could or would accept
Genetic Ancestry Strongly Impacts MAPT (17q21.31) Haplotype Frequencies of South American Populations
No full textGenetic and archaeological studies indicate that the American continent has undergone multiple waves of human migration, shaping a complex population genetic structure comprising three major ethnic groups—Native American, European, and African—unevenly distributed across the continent. In this study, we examined MAPT (17q21.31) haplotype and sub-haplotype frequencies by analyzing two SNP markers (rs10514879 and rs199451) in three South American groups from distinct countries: Waorani (Ecuadorian Amazon), Jujuy (Northwestern Argentina), and Afro-Colombian (Northwestern Colombia). To broaden the scope, we also genotyped four short tandem repeats (STRs) within the 17q21.31 chromosomal region and compiled H2 haplotype and sub-haplotype frequency data for 97 worldwide populations (Africa: 26; Asia: 37; Europe: 19; America: 15). We used the publicly available genome-wide databases 1000G and ALFRED. Genetic heterogeneity among population clusters, classified by geographic region, was examined by hierarchical AMOVA. Likewise, we explored genetic affinities between the Waorani, Afro-Colombian, and Jujuy samples and worldwide collections using factorial correspondence analysis (FCA). The H1 haplotype predominated in all study populations. Notably, H2 varied among them: in Afro-Colombians, H2 was found at a frequency of 0.058, with equal representation of sub-haplotypes H2’ and H2D. Among Native American groups (Waorani and Jujuy), the H2 haplotype was virtually absent, with only H2D detected in Jujuy at a very low frequency (0.007). Analysis of a set of STRs from the MAPT region identified distinct genetic features in Native American groups, characterized by markedly low heterozygosity. Waorani and Karitiana exhibited strikingly low genetic diversity, reflecting a significant degree of population isolation and, consequently, a potentially strong impact of genetic drift. In summary, our analyses demonstrate the utility of MAPT haplotypes in detecting the effects of population isolation, genetic drift, and admixture on the gene pool of the South American samples examined. MAPT haplotypes may serve as reliable lineage markers, given their ability to differentiate ethnic groups and trace ancestral chromosomes. They have proved to be informative and cost-effective tool for exploring ancestry, geographic origins, and demographic history in anthropological studies
Quantifying The Ecotoxicological Effects Of Harmful Algal Blooms On Vulnerable Native Amphibians
No full textHarmful algal blooms are a growing threat to freshwater habitats around the globe. The causative agents, cyanobacteria, may or may not release deadly toxins as they take over. These toxins are known to cause illness and even death in fish, birds, and mammals including humans; however, little is known about their impact on keystone, semiaquatic amphibian species. In this work I holistically evaluated species vulnerability, spatial and temporal interactions, and developmental effects of HABs and native amphibians in Michigan through a series of theoretical, field, and laboratory experiments. Using a novel trait-based ecological risk assessment framework, I identified trends in individual, population, and species level HAB vulnerability across Michigan’s 23 native amphibians. Most low-risk taxa scored consistently across individual, population, and species scales; whereas higher risk taxa scores were more volatile and often strongly influenced by species-level measures of high resiliency. I then evaluated historic and ongoing interactions between these species by comparing spatial and temporal overlap from state HAB surveys, amphibian community science records, and simple field surveys. I identified August and September as periods of major overlap in HAB occurrence and amphibian observation and development. Spatial hotspots for toxic HABs and amphibian observation were limited, but I recorded signs of Rana clamitans breeding activity in 52% of historic HAB lakes including 3 lakes with ongoing toxic blooms. Finally, I designed a repeat exposure experiment to determine the impact of cyanotoxins on embryonic and larval R. clamitans growth and development. After field collecting frog eggs and cyanobacteria cultures, I observed accelerated hatch rates in animals exposed to the high concentration of cyanobacteria extracts after 2 days. Animals were retained and maintained in non-toxic media with regular husbandry to allow for standard development. After this holding period, tadpoles were re-exposed to cyanobacteria solutions that were the same or slightly modified from the primary exposure. In these cases, previous exposure to low levels of microcystin as embryos limited growth as tadpoles, but other carry over effects from high concentration exposures were not observed. In all tadpoles exposed to 100 µg/L microcystins, accelerated growth and development was measured. Across all embryonic and larval exposures, fewer than 5% of animals died, which suggests that microcystins may not be lethal over high, chronic exposures in developing R. clamitans. Results from this research collectively suggest that HABs pose a risk to many species of amphibians in early stages of development and that more research is needed to elucidate the mechanisms and eventual trade-offs of the developmental plasticity observed in my final experiments. My research contributes novel methodologies for risk assessment and experimental assays that may be used by other scientists to responsibly fill the large gap in understanding this stressor. These findings support some previous work that indicate HABs as sublethal stressors in developing amphibian species. This collective work can be used to predict, quantify, and respond to growing threat of HABs in freshwater habitats to protect vulnerable populations
From Bedside To Bench: Investigating Retinal Regeneration In Zebrafish And Employing New Techniques To Study Human Retinal Pathology
No full textHumans have been fascinated by vision science and understanding how we perceive the world differently for centuries, with some of the earliest reports of inherited visual deficits in humans dating back to the 1700’s. Since that time, the exponential advancement of scientific knowledge has led us to a deep understanding of the molecular and cellular functionality of the visual system, from invertebrates to humans and everything in-between. One organism that has become the subject of intense research over the past two decades for its remarkable ability to regenerate its retina is the zebrafish. In response to acute damage in the zebrafish retina, a resident macroglia cell conserved in all vertebrate retinas, Müller glia, undergo a de-differentiation event and are capable of producing progenitor cells that will repopulate the entire adult retina. Müller glia have been studied in several contexts of retinal biology, in the context of maintaining retinal homeostasis and protecting the retina from insults, for their ability to regenerate the retina in some permissive species, and in their contributions to retinal pathology. With the original research described in this dissertation, I highlight three different research models that demonstrate the wide array of functionality and diversity of Müller glia in the retina, while also characterizing consequences of their activity on other resident cell types. I describe three properties of the Müller glia we have been characterizing in the Thummel Lab in which Müller glia “save the day” by regenerating in response to acute phototoxic lesion (Chapter 1), when they “fail to play” in response to a recently developed model of chronic low light exposure (Chapter 2), and when they “go astray” as demonstrated by their prominence in pathological epiretinal membrane specimens (Chapter 3). I then describe some of the ongoing characterization studies on the aging retina in the regenerative capable zebrafish, as well as future directions for functional studies to further characterize the pathways governing proper photoreceptor differentiation in the regeneration model. Lastly, future directions to elucidate the pathogenic mechanisms underlying human epiretinal membrane development is discussed
A Relational Learning Paradigm And Cognitive Functioning In Young Adults
No full textThis study explores the relationship between relational learning, as framed by Relational Frame Theory (RFT), and general cognitive functioning, specifically fluid reasoning (Gf) and crystallized knowledge (Gc). A sample of 72 healthy young adults aged 18–30 participated in a computer-based stimulus equivalence task. The task assessed relational learning across two conditions: familiar letters and novel abstract symbols, measuring accuracy, response times, and throughput. Participants also completed standardized cognitive assessments from the Woodcock-Johnson IV battery, providing indices of Gf, Gc, and processing speed (Gs).
Results revealed that Gf was the strongest predictor of relational learning accuracy, particularly in conditions requiring novel problem-solving, such as abstract symbol relations. Conversely, Gc showed weaker associations, primarily contributing to accuracy when familiar stimuli were used. Performance differed by relation type, with trained relations being more easily mastered compared to derived (mutually entailed or combinatorial) relations. Notably, derived relations were more strongly linked to Gf, highlighting the role of abstract reasoning in higher-order relational learning.
This research enriches the empirical basis for RFT by quantifying how fundamental cognitive abilities predict relational learning. Findings suggest that relational learning tasks may serve as sensitive neuropsychological measures of cognitive functioning and have potential applications in clinical assessments and interventions, particularly in populations with developmental or cognitive impairments. Future research should explore the implications of these findings across the lifespan and in diverse clinical populations