http://www.rssboard.org/rss-specification 720 https://escholarship.org/uc/ucsced_oapdeposits/rss Recent eScholarship items from Open Access Policy Deposits Mon, 22 Jun 2026 08:13:12 +0000 https://escholarship.org/uc/item/90b8x3jk This study examines how 1.5- and second-generation Muslim undergraduates in the United States make meaning of higher education amid the competing demands of displacement, racialized belonging, neoliberal aspiration, and Islamic ethical commitment. Drawing on ethnographic fieldwork and life history interviews with 20 Muslim students, I use an arrivant framework to analyze how the conditions of migration, empire, and racial capitalism shape students’ relationships to education. The findings reveal that arrivant Muslim students do not simply absorb or resist neoliberal educational logics but rework them through familial narratives of displacement, gendered constructions of cultural authenticity, and moral reasoning rooted in Islamic traditions. Students invoke American exceptionalist discourses of opportunity while contending with anti-Muslim racism, surveillance, and conditional belonging. Rather than treating educational aspiration as a cultural trait of immigrant families, this... https://escholarship.org/uc/item/90b8x3jk Sun, 7 Jun 2026 00:00:00 +0000 Ali, Arshad I https://escholarship.org/uc/item/93q1035t Disabled students have historically been dehumanized in education, generally, and in research and practice related to school mathematics (K–12), particularly. Typically, they are only offered access to low-rigor school mathematics emphasizing rote procedures and narrow skills, often segregated physically and socially from their nondisabled peers. Educators are crucial to the humanization of disabled students via anti-ableist and antiracist work toward systemic transformation. The purpose of this review is to take stock of the current knowledge base of educator and disability research concerning school mathematics, recommending directions for humanizing future research and practice. Through a humanizing mathematics education lens, we analyze 61 articles involving educators, disabilities, and school mathematics published during the decade between 2007 and 2016. Results of our analysis point to not only the continued perpetuation of dehumanizing approaches and positioning but also... https://escholarship.org/uc/item/93q1035t Thu, 21 Aug 2025 00:00:00 +0000 Tan, Paulo Padilla, Alexis Lambert, Rachel https://escholarship.org/uc/item/87m1z4cq This essay articulates an innovative counterstory-based methodology of decolonialde linking which disrupts the very epistemic foundations of sociological disciplinary boundaries and ways of thinking about the production and distribution of knowledges. As non-white co-authors, we have opted to follow to adopt an expansive conception of decolonial/border-thinking gnosis and delinking as a way to embrace all knowledges, particularly those which do not conform to disciplinary modes of exposition and rationalist systematicity within the epistemic conceptions of knowledge. Using two disabled counterstories as gnosis illustrations, our essay shows how their enactment transgresses established norms for addressing and engaging with traditional, discipline-bound epistemological concerns. As such, we aim to open theoretical and methodological avenues for decolonial and non-Eurocentric spheres of imagination. More specifically, since the worlds of mathematics and mathematics education are... https://escholarship.org/uc/item/87m1z4cq Thu, 21 Aug 2025 00:00:00 +0000 Padilla, Alexis Tan, Paulo https://orcid.org/0000-0002-0179-8048 https://escholarship.org/uc/item/02z1x1np This study employed an A-B singled subject design to explore the extent to which a peer-mediated intervention supported a first-grade student with autism's usage both in purpose and frequency of a speech-generating device (SGD) during mathematics activities. The intervention involved teaching a peer without a disability to encourage the student with autism to use the SGD during partnered mathematics activities. Our analysis involved visual and descriptive examination of trends and patterns over time, and comparison of means between and within phases. We found during the course of this study that (1) the student with autism's level of overall communication, which included the relevancy of these communicative behaviors, increased; (2) the student with autism's level of spontaneous communication acts increased; and (3) the peer became more independent with supporting the student with autism's communication. Implications for future research and practice are provided. https://escholarship.org/uc/item/02z1x1np Thu, 21 Aug 2025 00:00:00 +0000 Tan, Paulo https://orcid.org/0000-0002-0179-8048 Alant, Erna https://escholarship.org/uc/item/9d19k6hm This case study uses a sociocultural perspective and the concept of appropriation (Newman, Griffin and Cole, 1989; Rogoff, 1990) to describe how a student learned to work with linear functions. The analysis describes in detail the impact that interaction with a tutor had on a learner, how the learner appropriated goals, actions, perspectives, and meanings that are part of mathematical practices, and how the learner was active in transforming several of the goals that she appropriated. The paper describes how a learner appropriated two aspects of mathematical practices that are crucial for working with functions (Breidenbach, Dubinsky, Nichols and Hawks, 1992; Even, 1990; Moschkovich, Schoenfeld and Arcavi, 1993; Schwarz and Yerushalmy, 1992; Sfard, 1992): a perspective treating lines as objects and the action of connecting a line to its corresponding equation in the form y = mx + b. I use examples from the analysis of two tutoring sessions to illustrate how the tutor introduced... https://escholarship.org/uc/item/9d19k6hm Sun, 15 Dec 2024 00:00:00 +0000 Moschkovich, Judit N https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/9c96040k Students often voice computations during group discussions of mathematics problems. Yet, this type of private speech has received little attention from mathematics educators or researchers. In this article use excerpts from middle school students' group mathematical discussions to illustrate and describe "computational private speech." We analyze four examples of computational private speech using lenses from neo-Vygotskian psychology, sociolinguistics, and distributed cognition. Our analyses of computational private speech challenge the individualistic developmental assumptions of some neo-Vygotskian theories of private speech, and we show how this form of private speech can serve socio-cognitive functions during group mathematical discussions. Copyright © Regents of the University of California on behalf of the Laboratory of Comparative Human Cognition. https://escholarship.org/uc/item/9c96040k Sun, 15 Dec 2024 00:00:00 +0000 Zahner, William Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/6754t8v2 Abstract: After four decades of research and development on language in mathematics classrooms, there is consensus that enhancing language is crucial for promoting students’ mathematics learning. After briefly sketching the theoretical contexts for work on this topic, in this paper we present six design principles for instruction that enhances language for mathematics learning. We then review the research that provides an empirical foundation for these principles, (a) concerning the design of learning environments to enhance language for mathematics learning and (b) on teaching practices (including teacher moves and classroom norms) involved in the enactment of those designed learning environments. Without claiming completeness, this review of the state of development and research shows that some aspects of design and instruction that enhance language for mathematics learning have been well researched, whereas research gaps for other aspects persist. https://escholarship.org/uc/item/6754t8v2 Sun, 15 Dec 2024 00:00:00 +0000 Erath, Kirstin Ingram, Jenni Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 Prediger, Susanne https://escholarship.org/uc/item/5fb3t2jx Using the academic literacy in mathematics framework to uncover multiple aspects of activity during peer mathematical discussions https://escholarship.org/uc/item/5fb3t2jx Sun, 15 Dec 2024 00:00:00 +0000 Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 Zahner, William https://escholarship.org/uc/item/4jj9544k This article reviews two sets of research studies from outside of mathematics education to consider how they may be relevant to the study of bilingual mathematics learners using two languages. The first set of studies is psycholinguistics experiments comparing monolinguals and bilinguals using two languages during arithmetic computation (language switching). The second set of studies is sociolinguistic research on young bilinguals using two languages during conversations (code switching). I use an example of a mathematical discussion between bilingual students to illustrate how sociolinguistics can inform analyses of bilingual mathematical conversations. © 2006 Springer Science+Business Media, Inc. https://escholarship.org/uc/item/4jj9544k Sun, 15 Dec 2024 00:00:00 +0000 Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/4cm490n4 Revisiting Early Research on Early Language and Number Names https://escholarship.org/uc/item/4cm490n4 Sun, 15 Dec 2024 00:00:00 +0000 Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/2df545ph We analyze how three seventh grade mathematics teachers from a majority Latino/a, linguistically diverse region of Texas taught the same lesson on interpreting graphs of motion as part of the Scaling Up SimCalc study (. Roschelle et al., 2010). The students of two of the teachers made strong learning gains as measured by a curriculum-aligned assessment, while the students of the third teacher were less successful. To investigate these different outcomes, we compare the teaching practices in each classroom, focusing on the teachers' use of class time and instructional format, their use of mathematical discourse practices in whole-class discussions, and their responses to student contributions. We show that the more successful teachers allowed time for students to use the curriculum and software and discuss it with peers, that they used formal mathematical discourse along with less formal language, and that they responded to student errors using higher-level moves. We conclude by... https://escholarship.org/uc/item/2df545ph Sun, 15 Dec 2024 00:00:00 +0000 Zahner, William Velazquez, Griselda Moschkovich, Judit https://orcid.org/0000-0003-1522-9337 Vahey, Phil Lara-Meloy, Teresa https://escholarship.org/uc/item/25t440dx The concept of scaffolding can be used to describe various types of adult guidance, in multiple settings, across different time scales. This article clarifies what we mean by scaffolding, considering several questions specifically for scaffolding in mathematics: What theoretical assumptions are framing scaffolding? What is being scaffolded? At what level is scaffolding implemented? What is the setting for scaffolding? And lastly, how can scaffolding manage the tension between providing appropriate calibrated support while also providing opportunities beyond learners’ current understandings? The paper describes how attention to mathematical practices can maintain a sociocultural theoretical framing for scaffolding and move scaffolding beyond procedural fluency. The paper first specifies the sociocultural theoretical assumptions framing the concept of scaffolding, with particular attention to mathematical practices. The paper provides three examples of scaffolding mathematical practices... https://escholarship.org/uc/item/25t440dx Sun, 15 Dec 2024 00:00:00 +0000 Moschkovich, Judit N https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/0729z3nw In this article, we share our views on language-diversity issues in research in mathematics education. We describe tensions, questions, and myths that we regularly face as researchers. We use similarities and differences in two settings (multilingual classrooms in South Africa and U.S. mathematics classrooms with Latino/a students) to illustrate the complexity of this work and illuminate research findings. https://escholarship.org/uc/item/0729z3nw Sun, 15 Dec 2024 00:00:00 +0000 Phakeng, Mamokgethi Setati Moschkovich, Judit N https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/1p23k76t The Language of Ideas and the Language of Display: Reconceptualizing “Academic Language” in Linguistically Diverse Classrooms https://escholarship.org/uc/item/1p23k76t Wed, 6 Nov 2024 00:00:00 +0000 Bunch, George C https://orcid.org/0009-0004-6321-2657 https://escholarship.org/uc/item/9x0611ck The purpose of this article is to investigate the multiple political histories that have coalesced to produce support for or resistance to the Oakland Unified School District’s full-service community schools policy. It analyzes oral history interview data from eight stakeholders who represent the district’s major constituencies to explore the reasons why each individual, positioned differently within the larger district system, may or may not support a seemingly democratic, community-based reform. Through their voices, the article explains how different constituencies can interpret an urban district’s policies and form community-based coalitions that either further or obstruct a democratic, equity-minded reform. https://escholarship.org/uc/item/9x0611ck Mon, 29 Jul 2024 00:00:00 +0000 Trujillo, Tina M Hernández, Laura E Jarrell, Tonja Kissell, René https://orcid.org/0000-0002-1047-7262 https://escholarship.org/uc/item/9dj589s0 Coercion and consent for the U.S. education market: community engagement policy under racialized fiscal surveillance https://escholarship.org/uc/item/9dj589s0 Mon, 29 Jul 2024 00:00:00 +0000 Kissell, René Espinoza https://escholarship.org/uc/item/96z843z5 Purpose: This article investigates how school leaders make sense of social justice and democracy in their practice in two settings, a high-stakes testing and accountability context, the San Francisco Bay Area, California, and a low-stakes testing and accountability context, Norway. It demonstrates how leaders view relationships among education, democracy, and social justice, when located in a neoliberal democracy with a minimalist welfare state or in a social democracy with a robust welfare state. Design and Evidence: Through a comparative design, we analyze qualitative data from two international principal exchanges designed to capture outsiders’ impressions of schools in each context. Participants included alumni from an American and a Norwegian university’s principal preparation programs. Through preobservation and postobservation interviews and focus groups, we explore observations by practitioners, who acted as coconstructors in the research. Findings and Implications: The... https://escholarship.org/uc/item/96z843z5 Mon, 29 Jul 2024 00:00:00 +0000 Trujillo, Tina Møller, Jorunn Jensen, Ruth Kissell, René Espinoza Larsen, Eivind https://escholarship.org/uc/item/1sd2k2tk District leaders have rich insights into managing civic-minded reforms, like community schools, yet, little research on school reform examines their experiences within policy paradigms and political contexts that are increasingly marketized. Through oral histories with two longtime Oakland education leaders, we show how leaders negotiated and carried out initiatives while juggling challenges. Despite commitments to quality public education, leaders often faced competing pressures and values by local and external actors. We argue that Oakland represents a critical case of central office reform amid a resource-scarce, market-oriented educational landscape that shapes racialized community engagement and redefines power dynamics in the district. https://escholarship.org/uc/item/1sd2k2tk Mon, 29 Jul 2024 00:00:00 +0000 Kissell, René Espinoza https://orcid.org/0000-0002-1047-7262 Trujillo, Tina https://escholarship.org/uc/item/146933qm Takeover: Race, Education, and Democracy by Domingo Morel. New York: Oxford University Press, 2018. 206 pp., $105.00 (cloth). https://escholarship.org/uc/item/146933qm Mon, 29 Jul 2024 00:00:00 +0000 Trujillo, Tina Williams, Rachel E Kissell, René Espinoza https://orcid.org/0000-0002-1047-7262 https://escholarship.org/uc/item/8c89417b How can school mathematics prepare citizens for a democratic society? Answers to this question are not static; they change as society and its problems change. The SARS-CoV-2 pandemic with its corresponding disease COVID-19 presents such a problem: what is needed to navigate this complex situation that involves, among other things, mathematics? Using the essay genre, we use three narratives from three countries—Italy, the USA (California), and Germany—to reflect on the goals of teaching mathematics during this crisis and examine aspects of each country’s standards for mathematics education. These three stories are framed by the authors’ backgrounds, experiences, interests, their country’s situation, and response to the pandemic. We first present the three narratives and then examine common issues across them that might provide insights beyond this current crisis, for preparing students to become active citizens. In particular, we focus on three issues: (1) developing a positive... https://escholarship.org/uc/item/8c89417b Fri, 19 Jul 2024 00:00:00 +0000 Krause, Christina M Di Martino, Pietro Moschkovich, Judit N https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/5f4618cf Abstract: How do teachers develop and use political knowledge to create equitable and inclusive conditions for and with disabled students, particularly disabled students of color? In this essay, we build on concepts of political teacher knowledge in mathematics education, critical inclusive mathematics education and disability studies to explore teacher knowledges that support disabled students’ mathematical learning. We focus on four aspects of political knowledge for teaching mathematics: (1) knowledge as relational and unfolding over time, (2) understanding and negotiating the political contexts in which we teach mathematics, (3) deconstructing deficit discourses about marginalized students, and (4) learning to creatively resist the systems for and with our students. To develop our theoretical analysis, we use a counterstory of a middle school Latino student named Luis and his Latina mathematics teacher, Ms. Marquez. Our aim is to open up discussions in mathematics teacher... https://escholarship.org/uc/item/5f4618cf Fri, 19 Jul 2024 00:00:00 +0000 Padilla, Alexis Lambert, Rachel Tan, Paulo White-Smith, Kimberly https://escholarship.org/uc/item/49v5g90d A Naturalistic Paradigm: An Introduction to Using Ethnographic Methods for Research in Mathematics Education https://escholarship.org/uc/item/49v5g90d Fri, 19 Jul 2024 00:00:00 +0000 Moschkovich, Judit N https://orcid.org/0000-0003-1522-9337 https://escholarship.org/uc/item/2gv1p7tq (Fake) News is Racist: Mapping Culturally Relevant Approaches to Critical News Literacy Pedagogy https://escholarship.org/uc/item/2gv1p7tq Fri, 15 Sep 2023 00:00:00 +0000 Higdon, Nolan Butler, Allison https://escholarship.org/uc/item/00f3h5nh Time to put your marketing cap on: Mapping digital corporate media curriculum in the age of surveillance capitalism https://escholarship.org/uc/item/00f3h5nh Fri, 15 Sep 2023 00:00:00 +0000 Higdon, Nolan Butler, Allison https://escholarship.org/uc/item/8b48j712 <i>U2AF1</i> is one of the most recurrently mutated splicing factors in lung adenocarcinoma and has been shown to cause transcriptome-wide pre-mRNA splicing alterations; however, the full-length altered mRNA isoforms associated with the mutation are largely unknown. To better understand the impact <i>U2AF1</i> has on full-length isoform fate and function, we conducted high-throughput long-read cDNA sequencing from isogenic human bronchial epithelial cells with and without a <i>U2AF1 S34F</i> mutation. We identified 49,366 multi-exon transcript isoforms, more than half of which did not match GENCODE or short-read-assembled isoforms. We found 198 transcript isoforms with significant expression and usage changes relative to WT, only 68% of which were assembled by short reads. Expression of isoforms from immune-related genes is largely down-regulated in mutant cells and without observed splicing changes. Finally, we reveal that isoforms likely targeted by nonsense-mediated decay are... https://escholarship.org/uc/item/8b48j712 Sat, 9 Sep 2023 00:00:00 +0000 Soulette, Cameron M Hrabeta-Robinson, Eva Arevalo, Carlos Felton, Colette Tang, Alison D Marin, Maximillian G Brooks, Angela N https://orcid.org/0000-0002-7898-3073 https://escholarship.org/uc/item/8g23z97d The evolutionarily conserved splicing regulator neuro-oncological ventral antigen 1 (<i>NOVA1</i>) plays a key role in neural development and function. <i>NOVA1</i> also includes a protein-coding difference between the modern human genome and Neanderthal and Denisovan genomes. To investigate the functional importance of an amino acid change in humans, we reintroduced the archaic allele into human induced pluripotent cells using genome editing and then followed their neural development through cortical organoids. This modification promoted slower development and higher surface complexity in cortical organoids with the archaic version of <i>NOVA1</i> Moreover, levels of synaptic markers and synaptic protein coassociations correlated with altered electrophysiological properties in organoids expressing the archaic variant. Our results suggest that the human-specific substitution in <i>NOVA1</i>, which is exclusive to modern humans since divergence from Neanderthals, may have had functional... https://escholarship.org/uc/item/8g23z97d Fri, 16 Jun 2023 00:00:00 +0000 Trujillo, Cleber A Rice, Edward S Schaefer, Nathan K Chaim, Isaac A Wheeler, Emily C Madrigal, Assael A Buchanan, Justin Preissl, Sebastian Wang, Allen Negraes, Priscilla D Szeto, Ryan A Herai, Roberto H Huseynov, Alik Ferraz, Mariana SA Borges, Fernando S Kihara, Alexandre H Byrne, Ashley Marin, Maximillian Vollmers, Christopher https://orcid.org/0000-0002-7626-6222 Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Lautz, Jonathan D Semendeferi, Katerina Shapiro, Beth https://orcid.org/0000-0002-2733-7776 Yeo, Gene W Smith, Stephen EP Green, Richard E Muotri, Alysson R https://orcid.org/0000-0003-0867-2875 https://escholarship.org/uc/item/14t551dr The term “hybrid” emerged as a common descriptor of pandemic-modified schooling configurations. Yet this umbrella term insufficiently captures the variations among hybrid models, particularly as it pertains to the structure of teacher workdays and related workload demands. Drawing on qualitative research documenting K–12 U.S. teachers’ experience teaching during COVID-19, this brief introduces and explicates three terms specifying structural hybrid models—parallel, alternating, and blended—and their implications for teachers’ work. Differentiating among the models facilitates future analysis of the implications of hybrid schooling for teacher and student experience. Initial analysis indicates teachers experienced one model, blended hybrid, as more challenging than others. This teacher perception highlights the need to discern among the three hybrid models more closely when analyzing schools’ responses to the pandemic. Differentiating among hybrid models may prompt future analysis... https://escholarship.org/uc/item/14t551dr Fri, 9 Jun 2023 00:00:00 +0000 Bartlett, Lora https://escholarship.org/uc/item/9jt5h2hk A report of the Santa Clara County Teacher Workforce Study https://escholarship.org/uc/item/9jt5h2hk Wed, 7 Jun 2023 00:00:00 +0000 Tellez, Kip https://escholarship.org/uc/item/101965h5 SF3B1 is recurrently mutated in chronic lymphocytic leukemia (CLL), but its role in the pathogenesis of CLL remains elusive. Here, we show that conditional expression of Sf3b1-K700E mutation in mouse B cells disrupts pre-mRNA splicing, alters cell development, and induces a state of cellular senescence. Combination with Atm deletion leads to the overcoming of cellular senescence and the development of CLL-like disease in elderly mice. These CLL-like cells show genome instability and dysregulation of multiple CLL-associated cellular processes, including deregulated B cell receptor signaling, which we also identified in human CLL cases. Notably, human CLLs harboring SF3B1 mutations exhibit altered response to BTK inhibition. Our murine model of CLL thus provides insights into human CLL disease mechanisms and treatment. https://escholarship.org/uc/item/101965h5 Thu, 25 May 2023 00:00:00 +0000 Yin, Shanye Gambe, Rutendo G Sun, Jing Martinez, Aina Zurita Cartun, Zachary J Regis, Fara Faye D Wan, Youzhong Fan, Jean Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Herman, Sarah EM Hacken, Elisa ten Taylor-Weiner, Amaro Rassenti, Laura Z Ghia, Emanuela M https://orcid.org/0000-0002-6060-6106 Kipps, Thomas J https://orcid.org/0000-0002-0064-4549 Obeng, Esther A Cibulskis, Carrie L Neuberg, Donna Campagna, Dean R Fleming, Mark D Ebert, Benjamin L Wiestner, Adrian Leshchiner, Ignaty DeCaprio, James A Getz, Gad Reed, Robin Carrasco, Ruben D Wu, Catherine J Wang, Lili https://escholarship.org/uc/item/70g3v1fm The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected pervasive aberrant splicing as a characteristic feature of chronic lymphocytic leukemia (CLL), irrespective of splicing factor mutation status, which was associated with sensitivity to the spliceosome modulator, E7107. Splicing modulation affected CLL survival pathways, including members of the B cell lymphoma-2 (BCL2) family of proteins, remodeling antiapoptotic dependencies of human and murine CLL cells. E7107 treatment decreased myeloid cell leukemia-1 (MCL1) dependence and increased BCL2 dependence, sensitizing primary human CLL cells and venetoclax-resistant CLL-like cells from an Eμ-TCL1-based adoptive transfer murine model to treatment with the BCL2 inhibitor venetoclax. Our data provide preclinical rationale to support the combination of venetoclax with splicing modulators to reprogram apoptotic dependencies in CLL for treating venetoclax-resistant... https://escholarship.org/uc/item/70g3v1fm Tue, 23 May 2023 00:00:00 +0000 Hacken, Elisa ten Valentin, Rebecca Regis, Fara Faye D Sun, Jing Yin, Shanye Werner, Lillian Deng, Jing Gruber, Michaela Wong, Jessica Zheng, Mei Gill, Amy L Seiler, Michael Smith, Peter Thomas, Michael Buonamici, Silvia Ghia, Emanuela M https://orcid.org/0000-0002-6060-6106 Kim, Ekaterina Rassenti, Laura Z Burger, Jan A Kipps, Thomas J https://orcid.org/0000-0002-0064-4549 Meyerson, Matthew L Bachireddy, Pavan Wang, Lili Reed, Robin Neuberg, Donna Carrasco, Ruben D Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Letai, Anthony Davids, Matthew S Wu, Catherine J https://escholarship.org/uc/item/4d85s583 In eukaryotes, precursor mRNA (pre-mRNA) splicing removes non-coding intron sequences to produce mature mRNA. This removal is controlled in part by RNA-binding proteins that regulate alternative splicing decisions through interactions with the splicing machinery. RNA binding motif protein 25 (RBM25) is a putative splicing factor strongly conserved across eukaryotic lineages. However, the role of RBM25 in global splicing regulation and its cellular functions are unknown. Here we show that RBM25 is required for the viability of multiple human cell lines, suggesting that it could play a key role in pre-mRNA splicing. Indeed, transcriptome-wide analysis of splicing events demonstrated that RBM25 regulates a large fraction of alternatively spliced exons throughout the human genome. Moreover, proteomic analysis indicated that RBM25 interacts with components of the early spliceosome and regulators of alternative splicing. Previously, we identified an RBM25 species that is mono-methylated... https://escholarship.org/uc/item/4d85s583 Fri, 12 May 2023 00:00:00 +0000 Carlson, Scott M Soulette, Cameron M Yang, Ze Elias, Joshua E Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Gozani, Or https://escholarship.org/uc/item/3wg0q2db Targeting somatically activated oncogenes has revolutionized the treatment of non-small cell lung cancer (NSCLC). Mutations in the gene mesenchymal-epithelial transition (<i>MET</i>) near the exon 14 splice sites are recurrent in lung adenocarcinoma and cause exon skipping (<i>MET</i>Δ14). Here, we analyzed 4,422 samples from 12 different malignancies to estimate the rate of said exon skipping. <i>MET</i>Δ14 mutation and transcript were most common in lung adenocarcinoma. Endogenously expressed levels of METΔ14 transformed human epithelial lung cells in a hepatocyte growth factor-dependent manner. In addition, overexpression of the orthologous mouse allele induced lung adenocarcinoma in a novel, immunocompetent mouse model. Met inhibition showed clinical benefit in this model. In addition, we observed a clinical response to crizotinib in a patient with METΔ14-driven NSCLC, only to observe new missense mutations in the MET activation loop, critical for binding to crizotinib, upon... https://escholarship.org/uc/item/3wg0q2db Thu, 11 May 2023 00:00:00 +0000 Lu, Xinyuan Peled, Nir Greer, John Wu, Wei https://orcid.org/0000-0003-3938-8359 Choi, Peter Berger, Alice H Wong, Sergio Jen, Kuang-Yu https://orcid.org/0000-0003-2815-5912 Seo, Youngho https://orcid.org/0000-0001-5908-6636 Hann, Byron Brooks, Angela https://orcid.org/0000-0002-7898-3073 Meyerson, Matthew Collisson, Eric A https://escholarship.org/uc/item/81m0m09m Mutations in SF3B1, which encodes a spliceosome component, are associated with poor outcome in chronic lymphocytic leukemia (CLL), but how these contribute to CLL progression remains poorly understood. We undertook a transcriptomic characterization of primary human CLL cells to identify transcripts and pathways affected by SF3B1 mutation. Splicing alterations, identified in the analysis of bulk cells, were confirmed in single SF3B1-mutated CLL cells and also found in cell lines ectopically expressing mutant SF3B1. SF3B1 mutation was found to dysregulate multiple cellular functions including DNA damage response, telomere maintenance, and Notch signaling (mediated through KLF8 upregulation, increased TERC and TERT expression, or altered splicing of DVL2 transcript, respectively). SF3B1 mutation leads to diverse changes in CLL-related pathways. https://escholarship.org/uc/item/81m0m09m Sat, 6 May 2023 00:00:00 +0000 Wang, Lili Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Fan, Jean Wan, Youzhong Gambe, Rutendo Li, Shuqiang Hergert, Sarah Yin, Shanye Freeman, Samuel S Levin, Joshua Z Fan, Lin Seiler, Michael Buonamici, Silvia Smith, Peter G Chau, Kevin F Cibulskis, Carrie L Zhang, Wandi Rassenti, Laura Z Ghia, Emanuela M https://orcid.org/0000-0002-6060-6106 Kipps, Thomas J https://orcid.org/0000-0002-0064-4549 Fernandes, Stacey Bloch, Donald B Kotliar, Dylan Landau, Dan A Shukla, Sachet A Aster, Jon C Reed, Robin DeLuca, David S Brown, Jennifer R Neuberg, Donna Getz, Gad Livak, Kenneth J Meyerson, Matthew M Kharchenko, Peter V Wu, Catherine J https://escholarship.org/uc/item/5674v4wx Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer. https://escholarship.org/uc/item/5674v4wx Fri, 5 May 2023 00:00:00 +0000 Berger, Alice H Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Wu, Xiaoyun Shrestha, Yashaswi Chouinard, Candace Piccioni, Federica Bagul, Mukta Kamburov, Atanas Imielinski, Marcin Hogstrom, Larson Zhu, Cong Yang, Xiaoping Pantel, Sasha Sakai, Ryo Watson, Jacqueline Kaplan, Nathan Campbell, Joshua D Singh, Shantanu Root, David E Narayan, Rajiv Natoli, Ted Lahr, David L Tirosh, Itay Tamayo, Pablo Getz, Gad Wong, Bang Doench, John Subramanian, Aravind Golub, Todd R Meyerson, Matthew Boehm, Jesse S https://escholarship.org/uc/item/8390w0hj Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We&nbsp;performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung&nbsp;squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available... https://escholarship.org/uc/item/8390w0hj Sat, 8 Apr 2023 00:00:00 +0000 Hoadley, Katherine A Yau, Christina Wolf, Denise M Cherniack, Andrew D Tamborero, David Ng, Sam Leiserson, Max DM Niu, Beifang McLellan, Michael D Uzunangelov, Vladislav Zhang, Jiashan Kandoth, Cyriac Akbani, Rehan Shen, Hui Omberg, Larsson Chu, Andy Margolin, Adam A Veer, Laura J van’t Lopez-Bigas, Nuria Laird, Peter W Raphael, Benjamin J Ding, Li Robertson, A Gordon Byers, Lauren A Mills, Gordon B Weinstein, John N Van Waes, Carter Chen, Zhong Collisson, Eric A Network, The Cancer Genome Atlas Research Benz, Christopher C Perou, Charles M Stuart, Joshua M https://escholarship.org/uc/item/5kk2153s Current clinical practice is organized according to tissue or organ of origin of tumors. Now, The Cancer Genome Atlas (TCGA) Research Network has started to identify genomic and other molecular commonalities among a dozen different types of cancer. Emerging similarities and contrasts will form the basis for targeted therapies of the future and for repurposing existing therapies by molecular rather than histological similarities of the diseases. https://escholarship.org/uc/item/5kk2153s Sun, 2 Apr 2023 00:00:00 +0000 Chang, Kyle Creighton, Chad J Davis, Caleb Donehower, Lawrence Drummond, Jennifer Wheeler, David Ally, Adrian Balasundaram, Miruna Birol, Inanc Butterfield, Yaron SN Chu, Andy Chuah, Eric Chun, Hye-Jung E Dhalla, Noreen Guin, Ranabir Hirst, Martin Hirst, Carrie Holt, Robert A Jones, Steven JM Lee, Darlene Li, Haiyan I Marra, Marco A Mayo, Michael Moore, Richard A Mungall, Andrew J Robertson, A Gordon Schein, Jacqueline E Sipahimalani, Payal Tam, Angela Thiessen, Nina Varhol, Richard J Beroukhim, Rameen Bhatt, Ami S Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Cherniack, Andrew D Freeman, Samuel S Gabriel, Stacey B Helman, Elena Jung, Joonil Meyerson, Matthew Ojesina, Akinyemi I Pedamallu, Chandra Sekhar Saksena, Gordon Schumacher, Steven E Tabak, Barbara Zack, Travis Lander, Eric S Bristow, Christopher A Hadjipanayis, Angela Haseley, Psalm Kucherlapati, Raju Lee, Semin Lee, Eunjung Luquette, Lovelace J Mahadeshwar, Harshad S Pantazi, Angeliki Parfenov, Michael Park, Peter J Protopopov, Alexei Ren, Xiaojia Santoso, Netty Seidman, Jonathan Seth, Sahil Song, Xingzhi Tang, Jiabin Xi, Ruibin Xu, Andrew W Yang, Lixing Zeng, Dong Auman, J Todd Balu, Saianand Buda, Elizabeth Fan, Cheng Hoadley, Katherine A Jones, Corbin D Meng, Shaowu Mieczkowski, Piotr A Parker, Joel S Perou, Charles M Roach, Jeffrey Shi, Yan Silva, Grace O Tan, Donghui Veluvolu, Umadevi Waring, Scot Wilkerson, Matthew D Wu, Junyuan Zhao, Wei Bodenheimer, Tom Hayes, D Neil Hoyle, Alan P Jeffreys, Stuart R Mose, Lisle E Simons, Janae V Soloway, Mathew G Baylin, Stephen B Berman, Benjamin P Bootwalla, Moiz S Danilova, Ludmila Herman, James G https://escholarship.org/uc/item/3pv8c0gr While advancements in genome sequencing have identified millions of somatic mutations in cancer, their functional impact is poorly understood. We previously developed the expression-based variant impact phenotyping (eVIP) method to use gene expression data to characterize the function of gene variants. The eVIP method uses a decision tree-based algorithm to predict the functional impact of somatic variants by comparing gene expression signatures induced by introduction of wild-type (WT) versus mutant cDNAs in cell lines. The method distinguishes between variants that are gain-of-function, loss-of-function, change-of-function, or neutral. We present eVIP2, software that allows for pathway analysis (eVIP Pathways) and usage with RNA-seq data. To demonstrate the eVIP2 software and approach, we characterized two recurrent frameshift variants in RNF43, a negative regulator of Wnt signaling, frequently mutated in colorectal, gastric, and endometrial cancer. RNF43 WT, RNF43 R117fs, RNF43... https://escholarship.org/uc/item/3pv8c0gr Mon, 4 Oct 2021 00:00:00 +0000 Thornton, Alexis M Fang, Lishan Lo, April McSharry, Maria Haan, David O’Brien, Casey Berger, Alice H Giannakis, Marios Brooks, Angela N https://orcid.org/0000-0002-7898-3073 https://escholarship.org/uc/item/0668z5cx Determining the layers of gene regulation within the innate immune response is critical to our understanding of the cellular responses to infection and dysregulation in disease. We identified a conserved mechanism of gene regulation in human and mouse via changes in alternative first exon (AFE) usage following inflammation, resulting in changes to the isoforms produced. Of these AFE events, we identified 95 unannotated transcription start sites in mice using a de novo transcriptome generated by long-read native RNA-sequencing, one of which is in the cytosolic receptor for dsDNA and known inflammatory inducible gene, <i>Aim2</i>. We show that this unannotated AFE isoform of <i>Aim2</i> is the predominant isoform expressed during inflammation and contains an iron-responsive element in its 5'UTR enabling mRNA translation to be regulated by iron levels. This work highlights the importance of examining alternative isoform changes and translational regulation in the innate immune response... https://escholarship.org/uc/item/0668z5cx Thu, 2 Sep 2021 00:00:00 +0000 Robinson, Elektra K Jagannatha, Pratibha Covarrubias, Sergio Cattle, Matthew Smaliy, Valeriya Safavi, Rojin Shapleigh, Barbara Abu-Shumays, Robin Jain, Miten Cloonan, Suzanne M Akeson, Mark Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Carpenter, Susan https://orcid.org/0000-0002-5600-5404 https://escholarship.org/uc/item/3v83583v High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3′ poly(A) tail length, base modifications and transcript haplotypes. https://escholarship.org/uc/item/3v83583v Tue, 5 Jan 2021 00:00:00 +0000 Workman, Rachael E Tang, Alison D Tang, Paul S Jain, Miten Tyson, John R Razaghi, Roham Zuzarte, Philip C Gilpatrick, Timothy Payne, Alexander Quick, Joshua Sadowski, Norah Holmes, Nadine de Jesus, Jaqueline Goes Jones, Karen L Soulette, Cameron M Snutch, Terrance P Loman, Nicholas Paten, Benedict Loose, Matthew Simpson, Jared T Olsen, Hugh E Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Akeson, Mark Timp, Winston https://escholarship.org/uc/item/47w3w84w Enhancing the efficacy of proteasome inhibitors (PI)&nbsp;is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with&nbsp;the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality... https://escholarship.org/uc/item/47w3w84w Mon, 10 Aug 2020 00:00:00 +0000 Huang, Hector H Ferguson, Ian D Thornton, Alexis M Bastola, Prabhakar Lam, Christine Lin, Yu-Hsiu T Choudhry, Priya Mariano, Margarette C Marcoulis, Makeba D Teo, Chin Fen Malato, Julia Phojanakong, Paul J Martin, Thomas G Wolf, Jeffrey L Wong, Sandy W Shah, Nina Hann, Byron Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Wiita, Arun P https://escholarship.org/uc/item/3nm2p0sh The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements... https://escholarship.org/uc/item/3nm2p0sh Mon, 15 Jun 2020 00:00:00 +0000 Zhang, Yiqun Chen, Fengju Fonseca, Nuno A He, Yao Fujita, Masashi Nakagawa, Hidewaki Zhang, Zemin Brazma, Alvis Creighton, Chad J https://escholarship.org/uc/item/7rs0t4qr Homologue synapsis is required for meiotic chromosome segregation, but how synapsis is initiated between chromosomes is poorly understood. In Caenorhabditis elegans, synapsis and a checkpoint that monitors synapsis depend on pairing centers (PCs), cis-acting loci that interact with nuclear envelope proteins, such as SUN-1, to access cytoplasmic microtubules. Here, we report that spindle assembly checkpoint (SAC) components MAD-1, MAD-2, and BUB-3 are required to negatively regulate synapsis and promote the synapsis checkpoint response. Both of these roles are independent of a conserved component of the anaphase-promoting complex, indicating a unique role for these proteins in meiotic prophase. MAD-1 and MAD-2 localize to the periphery of meiotic nuclei and interact with SUN-1, suggesting a role at PCs. Consistent with this idea, MAD-1 and BUB-3 require full PC function to inhibit synapsis. We propose that SAC proteins monitor the stability of pairing, or tension, between homologues... https://escholarship.org/uc/item/7rs0t4qr Thu, 21 May 2020 00:00:00 +0000 Bohr, Tisha Nelson, Christian R Klee, Erin Bhalla, Needhi https://orcid.org/0000-0002-6859-0073 https://escholarship.org/uc/item/55q5k9pq The spindle checkpoint acts during cell division to prevent aneuploidy, a hallmark of cancer. During checkpoint activation, Mad1 recruits Mad2 to kinetochores to generate a signal that delays anaphase onset. Yet, whether additional factors contribute to Mad2's kinetochore localization remains unclear. Here, we report that the conserved AAA+ ATPase TRIP13(PCH-2) localizes to unattached kinetochores and is required for spindle checkpoint activation in Caenorhabditis elegans. pch-2 mutants effectively localized Mad1 to unattached kinetochores, but Mad2 recruitment was significantly reduced. Furthermore, we show that the C. elegans orthologue of the Mad2 inhibitor p31(comet)(CMT-1) interacts with TRIP13(PCH-2) and is required for its localization to unattached kinetochores. These factors also genetically interact, as loss of p31(comet)(CMT-1) partially suppressed the requirement for TRIP13(PCH-2) in Mad2 localization and spindle checkpoint signaling. These data support a model in... https://escholarship.org/uc/item/55q5k9pq Thu, 21 May 2020 00:00:00 +0000 Nelson, Christian R Hwang, Tom Chen, Pin-Hsi Bhalla, Needhi https://orcid.org/0000-0002-6859-0073 https://escholarship.org/uc/item/2gg6377p We present Butler, a computational tool that facilitates large-scale genomic analyses on public and academic clouds. Butler includes innovative anomaly detection and self-healing functions that improve the efficiency of data processing and analysis by 43% compared with current approaches. Butler enabled processing of a 725-terabyte cancer genome dataset from the Pan-Cancer Analysis of Whole Genomes (PCAWG) project in a time-efficient and uniform manner. https://escholarship.org/uc/item/2gg6377p Thu, 21 May 2020 00:00:00 +0000 Yakneen, Sergei Waszak, Sebastian M https://orcid.org/0000-0003-3042-9521 Gertz, Michael Korbel, Jan O https://escholarship.org/uc/item/22v640fr Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658&nbsp;whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5&nbsp;driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these... https://escholarship.org/uc/item/22v640fr Sat, 16 May 2020 00:00:00 +0000 Aaltonen, Lauri A Abascal, Federico Abeshouse, Adam Aburatani, Hiroyuki Adams, David J Agrawal, Nishant Ahn, Keun Soo Ahn, Sung-Min Aikata, Hiroshi Akbani, Rehan Akdemir, Kadir C Al-Ahmadie, Hikmat Al-Sedairy, T Al-Shahrour, Fatima Alawi, Malik Albert, Monique Aldape, Kenneth Alexandrov, Ludmil B Ally, Adrian Alsop, Kathryn Alvarez, Eva G Amary, Fernanda Amin, Samirkumar B Aminou, Brice Ammerpohl, Ole Anderson, Matthew J Ang, Yeng Antonello, Davide Anur, Pavana Aparicio, Samuel Appelbaum, Elizabeth L Arai, Yasuhito Aretz, Axel Arihiro, Koji Ariizumi, Shun-ichi Armenia, Joshua Arnould, Laurent Asa, Sylvia Assenov, Yassen Atwal, Gurnit Aukema, Sietse Auman, J Todd Aure, Miriam RR Awadalla, Philip Aymerich, Marta Bader, Gary D Baez-Ortega, Adrian Bailey, Matthew H Bailey, Peter J Balasundaram, Miruna Balu, Saianand Bandopadhayay, Pratiti Banks, Rosamonde E Barbi, Stefano Barbour, Andrew P Barenboim, Jonathan Barnholtz-Sloan, Jill Barr, Hugh Barrera, Elisabet Bartlett, John Bartolome, Javier Bassi, Claudio Bathe, Oliver F Baumhoer, Daniel Bavi, Prashant Baylin, Stephen B Bazant, Wojciech Beardsmore, Duncan Beck, Timothy A Behjati, Sam Behren, Andreas Niu, Beifang Bell, Cindy Beltran, Sergi Benz, Christopher Berchuck, Andrew Bergmann, Anke K Bergstrom, Erik N Berman, Benjamin P Berney, Daniel M Bernhart, Stephan H Beroukhim, Rameen Berrios, Mario Bersani, Samantha Bertl, Johanna Betancourt, Miguel Bhandari, Vinayak Bhosle, Shriram G Biankin, Andrew V Bieg, Matthias Bigner, Darell Binder, Hans Birney, Ewan Birrer, Michael Biswas, Nidhan K Bjerkehagen, Bodil Bodenheimer, Tom Boice, Lori Bonizzato, Giada De Bono, Johann S https://escholarship.org/uc/item/75h4z5j9 Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA... https://escholarship.org/uc/item/75h4z5j9 Fri, 23 Aug 2019 00:00:00 +0000 Collisson, Eric A Campbell, Joshua D Brooks, Angela N Berger, Alice H Lee, William Chmielecki, Juliann Beer, David G Cope, Leslie Creighton, Chad J Danilova, Ludmila Ding, Li Getz, Gad Hammerman, Peter S Neil Hayes, D Hernandez, Bryan Herman, James G Heymach, John V Jurisica, Igor Kucherlapati, Raju Kwiatkowski, David Ladanyi, Marc Robertson, Gordon Schultz, Nikolaus Shen, Ronglai Sinha, Rileen Sougnez, Carrie Tsao, Ming-Sound Travis, William D Weinstein, John N Wigle, Dennis A Wilkerson, Matthew D Chu, Andy Cherniack, Andrew D Hadjipanayis, Angela Rosenberg, Mara https://orcid.org/0000-0001-6400-3161 Weisenberger, Daniel J Laird, Peter W Radenbaugh, Amie Ma, Singer Stuart, Joshua M Averett Byers, Lauren Baylin, Stephen B Govindan, Ramaswamy Meyerson, Matthew Rosenberg, Mara Gabriel, Stacey B Cibulskis, Kristian Sougnez, Carrie Kim, Jaegil Stewart, Chip Lichtenstein, Lee Lander, Eric S Lawrence, Michael S Getz, Gad Kandoth, Cyriac Fulton, Robert Fulton, Lucinda L McLellan, Michael D Wilson, Richard K Ye, Kai Fronick, Catrina C Maher, Christopher A Miller, Christopher A Wendl, Michael C Cabanski, Christopher Ding, Li Mardis, Elaine Govindan, Ramaswamy Creighton, Chad J Wheeler, David Balasundaram, Miruna Butterfield, Yaron SN Carlsen, Rebecca Chu, Andy Chuah, Eric Dhalla, Noreen Guin, Ranabir Hirst, Carrie Lee, Darlene Li, Haiyan I Mayo, Michael Moore, Richard A Mungall, Andrew J Schein, Jacqueline E Sipahimalani, Payal Tam, Angela Varhol, Richard Gordon Robertson, A Wye, Natasja Thiessen, Nina Holt, Robert A Jones, Steven JM Marra, Marco A Campbell, Joshua D Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Chmielecki, Juliann Imielinski, Marcin Onofrio, Robert C Hodis, Eran Zack, Travis https://escholarship.org/uc/item/5dg5k95n The two studies reported on in this paper examine the features of words that distinguish students’ performances on vocabulary assessments as a means of understanding what contributes to the ease or difficulty of vocabulary knowledge. The two studies differ in the type of assessment, the types of words that were studied, and the grade levels and population considered. In the first study, an assessment of words that can be expected to appear with at least moderate frequency at particular levels of text was administered to students in grades 2 through 12. The second study considered the responses of fourth- and fifth-grade students, including English learners, to words that teachers had identified as challenging for those grade levels. The effects of the same set of word features on students’ vocabulary knowledge were examined in both studies: predicted appearances of a word and its immediate morphological family members, number of letters and syllables, dispersion across content... https://escholarship.org/uc/item/5dg5k95n Tue, 19 Mar 2019 00:00:00 +0000 Hiebert, Elfrieda Scott, Judith Castaneda, Ruben Spichtig, A https://escholarship.org/uc/item/5664w1xs Alternative splicing is regulated by RNA binding proteins (RBPs) that recognize pre-mRNA sequence elements and activate or repress adjacent exons. Here, we used RNA interference and RNA-seq to identify splicing events regulated by 56 Drosophila proteins, some previously unknown to regulate splicing. Nearly all proteins affected alternative first exons, suggesting that RBPs play important roles in first exon choice. Half of the splicing events were regulated by multiple proteins, demonstrating extensive combinatorial regulation. We observed that SR and hnRNP proteins tend to act coordinately with each other, not antagonistically. We also identified a cross-regulatory network where splicing regulators affected the splicing of pre-mRNAs encoding other splicing regulators. This large-scale study substantially enhances our understanding of recent models of splicing regulation and provides a resource of thousands of exons that are regulated by 56 diverse RBPs. https://escholarship.org/uc/item/5664w1xs Thu, 13 Sep 2018 00:00:00 +0000 Brooks, Angela N https://orcid.org/0000-0002-7898-3073 Duff, Michael O May, Gemma Yang, Li Bolisetty, Mohan Landolin, Jane Wan, Ken Sandler, Jeremy Booth, Benjamin W Celniker, Susan E Graveley, Brenton R Brenner, Steven E https://escholarship.org/uc/item/6c2423g7 In this ethnography of LGBTQ street youth, I argue that despite the regulation and containment of their bodies, queer street youth consistently create spaces of resistance that move them away from the tropes of infection, contamination, and deservedness that are inscripted onto the bodies of queer youth. Using the work of feminist philosopher Maria Lugones, this essay articulates a framework for resistance researchers - scholars who enact a "faithful witnessing" in solidarity with the communities they are describing, a movement away from the radical othering that often happens in social science research. It is in this positioning as a faithful witness that researchers can attend to the deconstruction of the discursive climates of deficit tropes that obscure the gestures and maneuvers of resistance. The tropes of contamination and irresponsibility intersect many of the experiences of LGBTQ street youth in ways that implicate not only LGBTQ street youth, but also other marginalized... https://escholarship.org/uc/item/6c2423g7 Tue, 19 Jun 2018 00:00:00 +0000 Cruz, Cindy https://escholarship.org/uc/item/2xs4870v This essay examines a video poem curriculum for Lesbian, Gay, Bisexual, Transgender, and Queer (LGBTQ) students of color at a continuation school in Los Angeles, California. In this close reading of a video poem that draws from a larger research project of a community-based learning curriculum, I have found that for LGBTQ students of color whose lives often intersect multiple oppressions, it is in the reflexive pedagogical work of "storying the self" (Goodson, 1998) where they develop a critical consciousness through an interrogation of their own bodies as they confront HIV, survival sex, and violence. The racially queered self/body, particularly in media work, becomes a rich representational tool used to facilitate reflection and praxical thinking about the multiple, often simultaneous experiences of Latino and African American LGBTQ students. It is in this pedagogical space where the urgency and necessity of a radical politic emerges from the analysis of intersection and intermeshment... https://escholarship.org/uc/item/2xs4870v Tue, 19 Jun 2018 00:00:00 +0000 Cruz, Cindy https://escholarship.org/uc/item/1ms339fb Testimonio, as a genre of the dispossessed, the migrant, and the queer, is a response to larger discourses of nation-building and has the potential to undermine the larger narratives that often erase and make invisible the expendable and often disposable labor and experiences of immigrants, the working class, African Americans, and others. This essay explores the use of testimonio in urban classrooms in Los Angeles and its use as a mediating tool in critical thinking and community based learning projects. I argue that there is a pedagogy to testimonio that is intersubjective and accessible and that, under certain circumstances, re-centers and revitalizes curriculum in this era of standardization and accountability, a hearkening to social justice movements that begin in education. © 2012 Copyright Taylor and Francis Group, LLC. https://escholarship.org/uc/item/1ms339fb Tue, 19 Jun 2018 00:00:00 +0000 Cruz, Cindy https://escholarship.org/uc/item/9wc6q7rf In Caenorhabditis elegans, germline apoptosis is promoted by egl-1 and ced-13 in response to meiotic checkpoint activation. We report that the requirement for these two factors depends on which checkpoints are active. We also identify a regulatory region of egl-1 required to inhibit germline apoptosis in response to DNA damage incurred during meiotic recombination. https://escholarship.org/uc/item/9wc6q7rf Thu, 22 Oct 2015 00:00:00 +0000 Ye, Alice L Ragle, J Matthew Conradt, Barbara Bhalla, Needhi https://orcid.org/0000-0002-6859-0073 https://escholarship.org/uc/item/6st9t1qd The Himalayan Kingdom of Bhutan, where images of magical splendor obscure its challenges, provides a viewpoint from which to understand the contradictions that emerging economies face as they move towards mass education. Isolated from the outside world in every sense except for the mythologies that surround it, Bhutan is attempting to move from a basic agrarian societal framework as found in the feudal 1800s into the whirl of a technologically savvy twenty-first century. The demands for such a transition require educators and politicians at all levels to rethink the role of schooling and what it means to be educated in this country at this point in time. To provide guidance, the government set up a special task force, the Royal Education Council, to devise a curriculum and pedagogy that would equip young people with the skills to move into the future without forsaking their past. This ethnographic piece of research explores the challenges faced by teachers and principals in nine... https://escholarship.org/uc/item/6st9t1qd Thu, 22 Oct 2015 00:00:00 +0000 Gordon, June A https://escholarship.org/uc/item/5rf804bt Chromosomes that fail to synapse during meiosis become enriched for chromatin marks associated with heterochromatin assembly. This response, called meiotic silencing of unsynapsed or unpaired chromatin (MSUC), is conserved from fungi to mammals. In Caenorhabditis elegans, unsynapsed chromosomes also activate a meiotic checkpoint that monitors synapsis. The synapsis checkpoint signal is dependent on cis-acting loci called Pairing Centers (PCs). How PCs signal to activate the synapsis checkpoint is currently unknown. We show that a chromosomal duplication with PC activity is sufficient to activate the synapsis checkpoint and that it undergoes heterochromatin assembly less readily than a duplication of a non-PC region, suggesting that the chromatin state of these loci is important for checkpoint function. Consistent with this hypothesis, MES-4 and MET-1, chromatin-modifying enzymes associated with transcriptional activity, are required for the synapsis checkpoint. In addition, a... https://escholarship.org/uc/item/5rf804bt Thu, 22 Oct 2015 00:00:00 +0000 Lamelza, Piero Bhalla, Needhi https://orcid.org/0000-0002-6859-0073 https://escholarship.org/uc/item/3b61n1wd © 2015 Elsevier Inc. This paper uses a sociocultural conceptual framework to provide an integrated view of academic literacy in mathematics for English Learners. The proposed definition of academic literacy in mathematics includes three integrated components: mathematical proficiency, mathematical practices, and mathematical discourse. The paper uses an analysis of a classroom discussion to illustrate how the three components of academic literacy in mathematics are intertwined, how academic literacy in mathematics is situated, and how participants engaged in academic literacy in mathematics use hybrid resources. The paper closes by describing the implications of this integrated view of academic literacy in mathematics for mathematics instruction for English Learners, arguing that it is important that the three components not be separated when designing instruction in general, and it is essential that mathematics instruction for English Learners address these three components simultaneo... https://escholarship.org/uc/item/3b61n1wd Thu, 22 Oct 2015 00:00:00 +0000 Moschkovich, Judit N https://escholarship.org/uc/item/3051n6g9 Meiotic chromosome segregation relies on homologous chromosomes being linked by at least one crossover, the obligate crossover. Homolog pairing, synapsis and meiosis specific DNA repair mechanisms are required for crossovers but how they are coordinated to promote the obligate crossover is not well understood. PCH-2 is a highly conserved meiotic AAA+-ATPase that has been assigned a variety of functions; whether these functions reflect its conserved role has been difficult to determine. We show that PCH-2 restrains pairing, synapsis and recombination in C. elegans. Loss of pch-2 results in the acceleration of synapsis and homolog-dependent meiotic DNA repair, producing a subtle increase in meiotic defects, and suppresses pairing, synapsis and recombination defects in some mutant backgrounds. Some defects in pch-2 mutants can be suppressed by incubation at lower temperature and these defects increase in frequency in wildtype worms grown at higher temperature, suggesting that PCH-2... https://escholarship.org/uc/item/3051n6g9 Thu, 22 Oct 2015 00:00:00 +0000 Deshong, Alison J Ye, Alice L Lamelza, Piero Bhalla, Needhi https://orcid.org/0000-0002-6859-0073 https://escholarship.org/uc/item/2bg0r9q0 Transnational migration is seldom associated with Japan even though Japan has been dependent on immigrants for several generations. The research presented in this article explores a reform effort viewed as radical within the Japanese context that took place in a metropolitan school known for having one of the largest number of immigrant students in Japan, most of whom hail from Latin America, Southeast Asia, and China. While many of these “Newcomers” are of Japanese ancestry, absence from the homeland for two to four generations has left them without the cultural and linguistic skills to navigate the nuances of Japanese society. As a result, schools, which have never had to respond to the needs of immigrant youth, find themselves at a loss as to how to integrate young people whose parents have been drawn back from the Japanese diaspora through government policies designed to assuage the labor shortage of the 1980s and 1990s. Over the course of 5&nbsp;months of ethnographic field... https://escholarship.org/uc/item/2bg0r9q0 Thu, 22 Oct 2015 00:00:00 +0000 Gordon, June A https://escholarship.org/uc/item/3nn1c8xs Mapping the Terrain: Language Testing and Placement for US-Educated Language Minority Students in California's Community Colleges [EXECUTIVE SUMMARY] https://escholarship.org/uc/item/3nn1c8xs Tue, 25 Jan 2011 00:00:00 +0000 Bunch, George Endris, Ann Panayotova, Dora Romero, Michelle Llosa, Lorena https://escholarship.org/uc/item/31m3q6tb Mapping the Terrain: Language Testing and Placement for US-Educated Language Minority Students in California's Community Colleges [FULL REPORT] https://escholarship.org/uc/item/31m3q6tb Tue, 25 Jan 2011 00:00:00 +0000 Bunch, George Endris, Ann Panayotova, Dora Romero, Michelle Llosa, Lorena https://escholarship.org/uc/item/10g691cw What's in a Test? ESL and English Placement Tests in California's Community Colleges and Implications for US-Educated Language Minority Students https://escholarship.org/uc/item/10g691cw Tue, 25 Jan 2011 00:00:00 +0000 Llosa, Lorena Bunch, George https://escholarship.org/uc/item/5fw380k7 Mathematics, Language, and Bilingual Latina/o Learners: A Review of the Empirical Research Literature https://escholarship.org/uc/item/5fw380k7 Fri, 29 Oct 2010 00:00:00 +0000 Moschkovich, Judit https://escholarship.org/uc/item/6x39n5kd C4 eJournal, Issue 1 https://escholarship.org/uc/item/6x39n5kd Wed, 27 May 2009 00:00:00 +0000 Bunch, George Wagoner, Richard L Santos, Jose L Melguizo, Tatiana