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\"The essays and entries in this book will allow us to see how history, politics, gender, race and class all affect the lives and practices of everyday citizens in Latin America and the Caribbean\"--Provided by publisher.

Abstract Identifying recurrent changes in biological sequences is important to multiple aspects of biological research—from understanding the molecular basis of convergent phenotypes, to pinpointing the causative sequence changes that give rise to antibiotic resistance and disease. Here, we present RECUR, a method for identifying recurrent amino acid substitutions from multiple sequence alignments that is fast, easy to use, and scalable to thousands of sequences. We demonstrate that RECUR's recurrence detection achieves 100% accuracy on simulated data with known evolutionary histories. We further show that RECUR is robust to realistic levels of tree inference error. Finally, we apply RECUR to a large set of surface glycoprotein (S) protein sequences from SARS-CoV-2. This analysis identified widespread recurrent evolution throughout the protein with significant enrichment in the exposed receptor-binding S1 subunit and at the interface with the human angiotensin-converting enzyme 2 (hACE2). In contrast, recurrent substitutions were depleted at the trimeric interface of the S protein. In silico modelling showed that recurrent substitutions had no directional effect on stability at either interface, but effects at the hACE2 interface were significantly more variable. Multiple substitutions with large destabilizing effects on hACE2 binding have been linked to immune escape, while others represented reversions back to the reference sequence, suggesting that recurrent evolution at this interface reflects opposing selective pressures balancing receptor binding with immune evasion. A standalone implementation of the algorithm is available under the GPLv3 license at https://github.com/OrthoFinder/RECUR.

Intra-arterial administration of melphalan chemotherapy has shown promise in the treatment of retinoblastoma. This report describes our results using superselective intra-arterial melphalan in patients with newly diagnosed retinoblastoma and those who were treated for progression after systemic chemotherapy. This is a retrospective review of all retinoblastoma patients treated with intra-arterial melphalan at the University of California, San Francisco from March 2010 to August 2012. Twenty eyes (16 patients) underwent 40 intra-arterial melphalan infusions, and dose was determined by age. Patients were treated at monthly intervals and received a range of 1-5 treatments. Response to therapy, toxicity, and procedural radiation exposure was assessed. All patients are alive without metastatic disease at a median follow-up of 14.5 (1-29) months. Treatment with enucleation or external beam radiation was avoided in 11/20 eyes (55%) overall [6/12 (50%) in newly diagnosed eyes and 5/8 (63%) in refractory/relapsed eyes]. Response rates (per the International Classification of Retinoblastoma) were as follows: 6/7 (86%) in groups A-C and 5/13 (38%) in groups D and E. Nonhematologic and hematologic toxicities were minimal and comparable with those in previous reports. The mean procedural radiation dose was 20.2 ± 11.9 mGy per eye per procedure. Superselective intra-arterial melphalan therapy is effective for less advanced eyes but further modifications to therapy are required to improve results in eyes with advanced retinoblastoma.

Breast cancers are complex cellular ecosystems where heterotypic interactions play central roles in disease progression and response to therapy. However, our knowledge of their cellular composition and organization is limited. Here we present a single-cell and spatially resolved transcriptomics analysis of human breast cancers. We developed a single-cell method of intrinsic subtype classification (SCSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) provides high-resolution immune profiles, including new PD-L1/PD-L2 + macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell-surface protein expression through differentiation within three major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into antitumor immune regulation. Using single-cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer. A multi-omic atlas of breast cancers, integrating single-cell RNA sequencing, spatial transcriptomics and immunophenotyping, identifies nine ecotypes associated with cellular heterogeneity and prognosis.

Mattering refers to the sense that one is significant and valued by others, which has been linked by a small but growing body of research to key work-related outcomes, including job satisfaction, organizational commitment, and job performance. This study examines mattering among Basic Science Medical Educators (BSME), a group potentially vulnerable to low workplace mattering due to limited leadership support and isolation from communities of practice. Consideration for follower well-being is important across many leadership theories, and transformational leadership behaviors overlap highly with behaviors thought to increase mattering. Survey responses from BSME and a general workforce sample were analyzed to assess the relationship between transformational leadership and five dimensions of mattering - general mattering, societal and interpersonal work mattering, and general and work anti-mattering - as well as job satisfaction, organizational commitment, and self-rated job performance. Transformational leadership significantly predicted all dimensions of mattering, particularly interpersonal work mattering. The effects of mattering on job satisfaction, organizational commitment, and performance were stronger than those of anti-mattering, suggesting that feeling valued has a greater impact on job attitudes than feeling invisible. Furthermore, interpersonal work mattering moderated the relationship between transformational leadership and job attitudes, amplifying its benefits. Notably, BSME felt their work was important to society regardless of their leadership. Overall, employee mattering is crucial in maximizing the benefits of transformational leadership, particularly among BSME.

American music education is focused primarily on music written by White men (Baker, 2003). However, women are more likely to believe they can find success in a career in the arts when they have positive female role models (Quimby & DeSantis, 2006). Similarly, college students are more likely to name career role models who match their own ethnicity (Karunanayake & Nuata, 2004). If young women and students of color do not get to see composers who remind them of themselves, then they will be less likely to feel confident as potential composers. The purpose of this study is to determine undergraduate music education students’ commitment to promoting the music of diverse composers in their future classrooms. A pilot study conducted in 2017 supported the need for this research. Participants in that study expressed the belief that composer diversity is important, but that their undergraduate program is not adequately preparing them to incorporate diverse composers in their teaching. The research addresses the following questions: 1) To what extent do preservice music teachers believe that composer diversity is important? 2) To what extent do preservice music teachers feel prepared to teach their students about diverse composers? 3) Are women preservice teachers and/or preservice teachers of color more likely to believe composer diversity is important than teachers who are men and/or White? All participants (n = 34) were junior and senior undergraduate students studying music education at a university in the mid-Atlantic states. These preservice music teachers completed an online survey, answering Likert-style questions about how they value composer diversity, and if they feel prepared to teach music written by composers of all genders and composers of color. They were also asked to name women composers, composers of color, and women composers of color they have studied in their undergraduate program. The participants’ responses were analyzed by gender and race, and the data was analyzed with a series of Kruskal-Wallis analysis of variance tests. The results of the study suggest that while preservice music teachers believe that teaching their students about diverse composers is important, they are not enthusiastic about how prepared they are to teach about these composers. They are especially unprepared to teach their students about women of color, suggesting a need for a more intersectional approach to diverse learning (Matsuda, 2013). No differences were found between participants of different races. There were no significant differences between gender nonbinary participants (n = 2) and participants of other genders. There were four significant differences between men (n = 19) and women (n = 13). Men responded with higher levels of agreement to the statements “I look forward to incorporating music by composers of color into my classroom” and “I look forward to incorporating music by composers of all genders into my classroom.” When asked about what factors influence their repertoire selection, women placed more importance on “The audience will enjoy the music” and “Composers of all genders are featured equally.” The median number of composers of color participants named was 5. The median number of female composers was 2.5, and the median number of female composers of color was 0.

Danio rerio zebrafish fins and human limbs, although outwardly dissimilar, develop using conserved genetic modules. However, unlike humans, zebrafish can perfectly regenerate their fins following amputation or injury. Therefore, understanding the mechanisms underlying fin development and regeneration may improve our understanding of human limb abnormalities and aid the rational design of therapeutics for injury repair. In this dissertation, I use the branched zebrafish caudal fin skeleton as a model system to explore the fundamental question of how appendages form a precisely patterned skeleton. Our lab previously discovered Sonic hedgehog (Shh) signaling is specifically required for fin ray branching during regeneration. In Chapter II, I extend this understanding to demonstrate Shh mediates ray branching during development of all seven zebrafish fins. Further, I find Shh slows the migration of basal epidermal cells as they pass over immature bone in the distal outgrowing fin. This reinforces a potential heterotypic cell association mechanism by which the Shh+ basal epidermis directs branching during ray formation. In Chapter III, I further detail the development of the caudal fin skeleton. I describe how a subset of fin rays, the peripheral principal rays, differs in ontogeny from other fin rays and propose three organizing centers together produce caudal fin symmetry. Chapter IV uses a zebrafish model of Fraser Syndrome to explore how basement membrane-mediated epithelial-mesenchymal associations contribute to ray branching morphogenesis in development and regeneration. In addition to describing the first adult zebrafish model of Fraser Syndrome, I characterize dramatic fin ray patterning abnormalities including but not limited to unbranched rays. I demonstrate the skeletal patterning abnormalities are Shh signaling-independent, showing the basement membrane (and likely additional extracellular structures) establishes a permissive environment for robust skeletal patterning. Turning back to which signals direct ray branching, I identify wnt10a, which is known to be expressed during fin regeneration, as a putative upstream activator of localized basal epidermal shha. In Chapter V, I generate fin-deficient wnt10a mutants and describe the temporal requirements of Wnt10a for median fin development and regeneration. In Chapter VI, I use the wnt10a mutants to demonstrate Wnt10a activates basal epidermal shha expression and thereby initiates the cooperative cell behaviors underlying ray branching morphogenesis. Collectively, this dissertation advances our understanding of the molecular control of zebrafish fin development, regeneration, and skeletal patterning.

This study provided a county-funded reentry resource management center located in Texas with evaluative strategies to ensure the implementation of evidence-based practices and effective use of funds. This research explored recidivism within a local jail setting. The researcher performed a critical analysis of the reentry center’s existing logic model in order to operationalize elements intended to accomplish the overall mission to reduce recidivism within the county. Staff interviews provided insight into perceptions of legitimacy toward the center’s mission, respective job-related duties, and the logic model. Finally, several quantitative analyses describe the demographic- and offense-related data of the client base, as well as recidivism rates compared to the general population in the local jail. The analyses performed found that outreach efforts target parolee populations rather than individuals serving time in the local jail. While causation cannot be concluded due to the referral-based services provided by the center’s staff, individuals who become clients were rearrested less often than non-clients. The study concludes with several recommendations for expanding outreach and recidivism data access as well as incorporating client feedback to better serve unique release populations.

The gut ecosystem is shaped by multiple factors with the immune system being one of the major determinants in shaping its composition in health and disease. On the other hand, the immune system regulates its responses through the action of the sympathetic nervous system (SNS) in part through beta-adrenergic receptors 1/2 (ADRB1/2). In the past years, a clear link has been established between the immune system, SNS, and the modification of nutrient absorption by the gut microbiota in the development of diet-induced obesity. We have previously shown in male mice transplanted with bone marrow cells ADRB1/2 knock-out mice (KD) showed mild immunosuppression and microbiota changes. Post-recovery, mice were challenged with high-fat diet (HFD) for two weeks . Our findings show that KD mice are protected against diet-induced adiposity and weight gain. Additionally, these mice showed an increase in residual calorific values and a decreased expression of the fatty acid transporter FAT/CD36. Suggesting a decreased absorption of lipids in the KD mice. Gut microbiota analysis showed that KD microbiota composition on a HFD remained stable with a significant enrichment in the , which is depleted in obesity. This was associated with a switch from triglycerides to diglyceride fecal profile. Moreover, microbiome culture showed a decrease in triglycerides after an incubation with 0.1% of HFD lipid extract. Suggesting a potential role of the in the metabolism of these lipids. Our findings demonstrate not only that the gut microbiota can modify nutrient absorption and susceptibility to diet-induced obesity but also that the immune system contributes to selective depletion of microbial members that would otherwise thrive on dietary lipids. Revealing a novel mechanism by which host immunity sculpts the gut ecosystem in ways that influence metabolic outcomes.