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Students are more likely to learn in college science, technology, engineering, and math (STEM) classrooms when instructors use teacher discourse moves (TDMs) that encourage student engagement and learning. However, although teaching practices are well studied, TDMs are not well understood in college STEM classrooms. In STEM courses at a minority-serving institution (MSI; n = 74), we used two classroom observation protocols to investigate teaching practices and TDMs across disciplines, instructor types, years of teaching experience, and class size. We found that instructors guide students in active learning activities, but they use authoritative discourse approaches. In addition, chemistry instructors presented more than biology instructors. Also, teaching faculty had relatively high dialogic, interactive discourse, and neither years of faculty teaching experience nor class size had an impact on teaching practices or TDMs. Our results have implications for targeted teaching professional development efforts across instructor and course characteristics to improve STEM education at MSIs.
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Romosozumab, a humanized monoclonal antibody specific for sclerostin (SOST), has been approved for treatment of postmenopausal women with osteoporosis at a high risk for fracture. Previous work in sclerostin global knockout (Sost-/-) mice indicated alterations in immune cell development in the bone marrow (BM), which could be a possible side effect in romosozumab-treated patients. Here, we examined the effects of short-term sclerostin depletion in the BM on hematopoiesis in young mice receiving sclerostin antibody (Scl-Ab) treatment for 6 weeks, and the effects of long-term Sost deficiency on wild-type (WT) long-term hematopoietic stem cells transplanted into older cohorts of Sost-/- mice. Our analyses revealed an increased frequency of granulocytes in the BM of Scl-Ab-treated mice and WTâSost-/- chimeras, indicating myeloid-biased differentiation in Sost-deficient BM microenvironments. This myeloid bias extended to extramedullary hematopoiesis in the spleen and was correlated with an increase in inflammatory cytokines TNFα, IL-1α, and MCP-1 in Sost-/- BM serum. Additionally, we observed alterations in erythrocyte differentiation in the BM and spleen of Sost-/- mice. Taken together, our current study indicates novel roles for Sost in the regulation of myelopoiesis and control of inflammation in the BM.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Medula Óssea/patologia , Inflamação/etiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Anticorpos Monoclonais , Medula Óssea/fisiologia , Citocinas , Feminino , Técnicas de Inativação de Genes , Células-Tronco Hematopoéticas , Inflamação/induzido quimicamente , Masculino , Camundongos , Camundongos Knockout , MielopoeseRESUMO
PURPOSE OF REVIEW: We reviewed recent progress on the role of sclerostin (SOST) and its effects on the immune system in order to summarize the current state of knowledge in osteoimmunology, in regard to hematopoiesis, lymphopoiesis, and inflammation. RECENT FINDINGS: Changes in sclerostin levels affect distinct niches within the bone marrow that support hematopoietic stem cells and B cell development. Sclerostin's regulation of adipogenesis could also be important for immune cell maintenance with age. Surprisingly, B cell development in the bone marrow is influenced by Sost produced by mesenchymal stem cells and osteoblasts, but not by osteocytes. Additionally, extramedullary hematopoiesis in the spleen and increased pro-inflammatory cytokine levels in the bone marrow are observed in global Sost-/- mice. In addition to changes in bone marrow density, sclerostin depletion affects B lymphopoiesis and myelopoiesis, as well as other changes within the bone marrow cavity that could affect hematopoiesis. It is therefore important to monitor for hematopoietic changes in patients receiving sclerostin-depleting therapies.
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Proteínas Adaptadoras de Transdução de Sinal/imunologia , Adipogenia/imunologia , Hematopoese Extramedular/imunologia , Linfopoese/imunologia , Animais , Linfócitos B , Medula Óssea/imunologia , Citocinas/imunologia , Hematopoese/imunologia , Células-Tronco Hematopoéticas , Humanos , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Knockout , Mielopoese/imunologia , Osteoblastos/imunologia , Osteócitos/imunologiaRESUMO
PURPOSE OF REVIEW: We reviewed the current literature on the roles of the Wnt antagonists sclerostin (Sost) and sclerostin-containing domain protein 1 (Sostdc1) on bone homeostasis, the relationship of the hypoxia-inducible factor (Hif) and von Hippel-Lindau (Vhl) pathways on Sost expression, and how changes in bone induced by depletion of Sost, Sostdc1, and Vhl affect hematopoietic cells. RECENT FINDINGS: B cell development is adversely affected in Sost-knockout mice and is more severely affected in Vhl-knockout mice. Inflammation in the Sost-/- bone microenvironment could alter hematopoietic stem cell behavior. Sostdc1-/- mice display defects in natural killer cell development and cytotoxicity. Depletion of Sost and Sostdc1 have effects on immune cell function that warrant investigation in patients receiving Wnt antagonist-depleting therapies for treatment of bone diseases. Additional clinical applications for manipulation of Wnt antagonists include cancer immunotherapies, stem cell transplantation, and directed differentiation to immune lineages.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Osso e Ossos/metabolismo , Hematopoese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Osso e Ossos/efeitos dos fármacos , Hematopoese/fisiologia , Células-Tronco Hematopoéticas , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Sistema Imunitário/citologia , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Camundongos , Esqueleto/citologia , Esqueleto/efeitos dos fármacos , Esqueleto/metabolismoRESUMO
Students at Minority-Serving Institutions (MSIs) faced significant hardships while trying to learn through emergency remote teaching (ERT) during the COVID-19 pandemic. Our research aims to investigate if science, technology, engineering, and mathematics (STEM) instructors thought about and enacted more learner-centered teaching practices to alleviate some of this stress encountered by their students. Using semi-structured interviews and classroom observations, we utilized inductive and deductive qualitative research methods to examine two questions: (1) To what extent were STEM instructor's perceived pedagogical changes learner-centered during ERT?; and (2) To what extent were STEM instructor's teaching behaviors and discourse practices learner-centered during ERT? Our findings revealed that during ERT, STEM instructors described using a variety of pedagogical changes that we identified as learner-centered under the Weimer framework, including ideas such as enacting flexible late policies and increased usage of formative assessment. Interestingly, we found that many of these learned-centered changes were happening outside of the classroom. Classroom observations assessing instructor behaviors and discourse demonstrated that STEM instructors enacted practices that aligned with Weimer's five constructs of learner-centered teaching. Our research highlights implications of learner-centered teaching practices for STEM instructors as well as researchers.
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COVID-19 , Educação a Distância , Pandemias , SARS-CoV-2 , Ciência , COVID-19/epidemiologia , Humanos , Ciência/educação , Estudantes/psicologia , Ensino , Docentes , Engenharia/educação , Aprendizagem , Tecnologia/educaçãoRESUMO
Instructor discourse, defined as verbal interactions with students in the classroom, can play an important role in student learning. Instructors who use dialogic discourse invite students to develop their own ideas, and both students and the instructor share ideas in back-and-forth exchanges. This type of discourse is well-suited to facilitate deep learning for students but is rare in undergraduate biology classrooms. Understanding the reasoning that underlies the use of dialogic discourse can inform teaching professional development for instructors who are learning to use discourse to support student learning. Through classroom video recordings to identify dialogic discourse and stimulated recall interviews to elicit instructor reasoning, we investigated why undergraduate biology instructors used dialogic discourse in active-learning lessons. Using inductive and deductive qualitative analysis of interview transcripts, we identified and characterized seven reasons that instructors used dialogic discourse, including three aligned with a theoretical framework of student cognitive engagement and four that emerged from our data set. In addition to aiming to prompt generative cognitive engagement in 34% of instances of dialogic discourse, instructors used dialogic discourse to prompt activity, supply information, provide feedback, decipher student thinking, leverage student thinking, and cue students to make connections. Reasoning varied across different types of dialogic discourse. These findings provide valuable insights that can inform research, teaching professional development, and individual instructors' reflections.
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In recent years, general hypoxia-inducible factor (HIF)-prolyl hydroxylase (PHD) enzyme inhibitors have been developed for the treatment of anemia due to renal disease and osteoporosis. However, it remains a challenge to target the HIF signaling pathway without dysregulating the skeletal and hematopoietic system. Here, we examined the effects of Vhl deletion in bone by performing longitudinal analyses of Vhl cKO mice at 3, 6, 10, and 24 weeks of age, where at 10 and 24 weeks of age, high bone mass and splenomegaly are present. Using flow cytometry, we observed increased frequency (%) of CD71 lo TER119 hi FSC lo orthochromatophilic erythroblasts and reticulocytes in 10- and 24-week-old Vhl cKO bone marrow (BM), which correlated with elevated erythropoietin levels in the BM and increased number of red blood cells in circulation. The absolute numbers of myeloerythroid progenitors (MEPs) in the BM were significantly reduced at 24 weeks. Bulk RNA-Seq of the MEPs showed upregulation of Epas1 ( Hif1a) and Efnb2 ( Hif2a) in Vhl cKO MEPs, consistent with a response to hypoxia, and genes involved in erythrocyte development, actin filament organization, and response to glucose. Additionally, histological analysis of Vhl cKO spleens revealed red pulp hyperplasia and the presence of megakaryocytes, both of which are features of extramedullary hematopoiesis (EMH). EMH in the spleen was correlated with the presence of mature stress erythroid progenitors, suggesting that stress erythropoiesis is occurring to compensate for the BM microenvironmental irregularities. Our studies implicate that HIF-driven alterations in skeletal homeostasis can accelerate erythropoiesis. Key Points: ⢠Dysregulation of HIF signaling in Dmp1+ bone cells induces stress erythropoiesis.⢠Skeletal homeostasis modulates erythropoiesis.
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While many STEM (science, technology, engineering, and mathematics) instructors returned to in-person instruction in fall 2021, others found themselves continuing to teach via online, hybrid, or hybrid flexible (i.e., hyflex) formats. Regardless of one's instructional modality, the findings from our own and other studies provided insight into effective strategies for increasing student engagement and decreasing cognitive overload. As part of this perspective, we included data from undergraduate students, many of whom are first generation and low income and from marginalized backgrounds, to identify instructional practices that helped them thrive and succeed during the recent COVID-19 pandemic. More specifically, we explored the various pedagogies and technologies utilized during emergency remote teaching to identify best practices as we considered the future of teaching. In sharing best practices at our institution, we aimed to provide a framework for deep reflection among the readers and the identification of practices to start, stop, and/or continue at their own institutions.
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[This corrects the article DOI: 10.1186/s40594-022-00335-1.].
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BACKGROUND: Due to the COVID-19 pandemic, many universities moved to emergency remote teaching (ERT). This allowed institutions to continue their instruction despite not being in person. However, ERT is not without consequences. For example, students may have inadequate technological supports, such as reliable internet and computers. Students may also have poor learning environments at home and may need to find added employment to support their families. In addition, there are consequences to faculty. It has been shown that female instructors are more disproportionately impacted in terms of mental health issues and increased domestic labor. This research aims to investigate instructors' and students' perceptions of their transition to ERT. Specifically, during the transition to ERT at a research-intensive, Minority-Serving Institution (MSI), we wanted to: (1) Identify supports and barriers experienced by instructors and students. (2) Compare instructors' experiences with the students' experiences. (3) Explore these supports and barriers within the context of social presence, teaching presence, and/or cognitive presence as well as how these supports and barriers relate to scaffolding in STEM courses. RESULTS: Instructors identified twice as many barriers as supports in their teaching during the transition to ERT and identified casual and formal conversations with colleagues as valuable supports. Emerging categories for barriers consisted of academic integrity concerns as well as technological difficulties. Similarly, students identified more barriers than supports in their learning during the transition to ERT. More specifically, students described pre-existing course structure, classroom technology, and community as best supporting their learning. Barriers that challenged student learning included classroom environment, student availability, and student emotion and comfort. CONCLUSIONS: Together, this research will help us understand supports and barriers to teaching and learning during the transition to ERT. This understanding can help us better plan and prepare for future emergencies, particularly at MSIs, where improved communication and increased access to resources for both students and instructors are key. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40594-022-00335-1.
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As part of the Reproducibility Project: Cancer Biology, we published Registered Reports that described how we intended to replicate selected experiments from 29 high-impact preclinical cancer biology papers published between 2010 and 2012. Replication experiments were completed and Replication Studies reporting the results were submitted for 18 papers, of which 17 were accepted and published by eLife with the rejected paper posted as a preprint. Here, we report the status and outcomes obtained for the remaining 11 papers. Four papers initiated experimental work but were stopped without any experimental outcomes. Two papers resulted in incomplete outcomes due to unanticipated challenges when conducting the experiments. For the remaining five papers only some of the experiments were completed with the other experiments incomplete due to mundane technical or unanticipated methodological challenges. The experiments from these papers, along with the other experiments attempted as part of the Reproducibility Project: Cancer Biology, provides evidence about the challenges of repeating preclinical cancer biology experiments and the replicability of the completed experiments.
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Pesquisa Biomédica/métodos , Neoplasias , Reprodutibilidade dos Testes , Animais , Linhagem Celular , Humanos , CamundongosRESUMO
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replications of selected experiments from a substantial number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012, were selected on the basis of citations and Altmetric scores (Errington et al., 2014). This Registered Report describes the proposed replication plan of experiments from "A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations" by Sharma and colleagues, published in Cell in 2010 (Sharma et al., 2010). Sharma and colleagues demonstrated that prolonged exposure of cancer cells to TKIs give rise to small populations of "drug tolerant persisters" (DTPs) (Figure 1B-C) that were reversed during subsequent maintenance under drug-free conditions (Figures 1E, 2B and 2E). DTPs exhibited reduced histone acetylation and sensitivity to HDAC inhibitors (HDIs) (Figure 4A-B). Drug sensitivity was restored with co-treatment of either HDIs or an IGF-1R inhibitor, in combination with TKIs (Figure 5A-B). Inhibition of IGF-1R activation also led to decreased KDM5A expression and restoration of H3K4 methylation, suggesting a direct link between the IGF-1R signaling pathway and KDM5A function (Figure 7A, 7C, and 7I). The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.