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  1. Article ; Online: The art of equity: critical health humanities in practice.

    Mathieu, Irène P / Martin, Benjamin J

    Philosophy, ethics, and humanities in medicine : PEHM

    2023  Volume 18, Issue 1, Page(s) 19

    Abstract: Background: The American Association of Medical Colleges has called for incorporation of the health humanities into medical education, and many medical schools now offer formal programs or content in this field. However, there is growing recognition ... ...

    Abstract Background: The American Association of Medical Colleges has called for incorporation of the health humanities into medical education, and many medical schools now offer formal programs or content in this field. However, there is growing recognition among educators that we must expand beyond empathy and wellness and apply the health humanities to questions of social justice - that is, critical health humanities. In this paper we demonstrate how this burgeoning field offers us tools for integrating social justice into medical education, utilizing the frameworks of critical consciousness and structural competency.
    Practice of health humanities: Critical health humanities can be applied at multiple levels of learners, and in a variety of contexts. We are two physician-writers who have developed several educational programs that demonstrate this. We taught a seminar that introduced first-year and second-year undergraduates to concepts such as social determinants of health, intergenerational trauma, intersectionality, resilience, and cross-cultural care through works of fiction, poetry, film, podcasts, stand-up comedy, and more. Through creative projects and empathic reflection, students engaged with the complexities of structural forces that create and maintain health disparities. Medical students in their clinical years can engage in critical health humanities learning experiences as well. We teach several multidisciplinary electives that address social (in)justice in medicine, as well as mentor fourth-year students engaged in independent electives that foster critical awareness around health equity and ethics. Beyond the classroom, we have actively engaged in critical health humanities practices through story slams, literary journal clubs, conference presentations, and Grand Rounds. Through these activities we have included learners at GME and CME levels. These examples also demonstrate how community engagement and multidisciplinary partnerships can contribute to the practice of critical health humanities.
    Conclusion: In this paper, we explore the growing field of critical health humanities and its potential for teaching health equity through narrative practices. We provide concrete examples of educational activities that incorporate critical consciousness and structural competency - frameworks we have found useful for conceptualizing critical health humanities as a pedagogical practice. We also discuss the strengths and challenges of this work and suggest future directions.
    MeSH term(s) Humans ; Curriculum ; Humanities/education ; Education, Medical ; Learning ; Medicine ; Education, Medical, Undergraduate
    Language English
    Publishing date 2023-12-13
    Publishing country England
    Document type Letter
    ZDB-ID 2229777-7
    ISSN 1747-5341 ; 1747-5341
    ISSN (online) 1747-5341
    ISSN 1747-5341
    DOI 10.1186/s13010-023-00149-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: ecDNA party bus: Bringing the enhancer to you.

    Adelman, Karen / Martin, Benjamin J E

    Molecular cell

    2021  Volume 81, Issue 9, Page(s) 1866–1867

    Abstract: Recent work from Zhu et al. (2021) reveals that extrachromosomal DNA circles harboring enhancers can serve as mobile regulatory elements that interact with chromosomal oncogenes, stimulating high-level gene activity and contributing to tumor ... ...

    Abstract Recent work from Zhu et al. (2021) reveals that extrachromosomal DNA circles harboring enhancers can serve as mobile regulatory elements that interact with chromosomal oncogenes, stimulating high-level gene activity and contributing to tumor heterogeneity and cancer progression.
    MeSH term(s) Carcinogenesis ; Chromosomes ; Humans ; Neoplasms/genetics ; Oncogenes ; Regulatory Sequences, Nucleic Acid
    Language English
    Publishing date 2021-05-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.04.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Reply to: Pitfalls in using phenanthroline to study the causal relationship between promoter nucleosome acetylation and transcription.

    Martin, Benjamin J E / Howe, LeAnn J

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 3725

    MeSH term(s) Acetylation ; Chromatin ; Histones/metabolism ; Nucleosomes/genetics ; Phenanthrolines ; Promoter Regions, Genetic ; Transcription, Genetic
    Chemical Substances Chromatin ; Histones ; Nucleosomes ; Phenanthrolines
    Language English
    Publishing date 2022-06-29
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-30351-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: ecDNA party bus: Bringing the enhancer to you

    Adelman, Karen / Martin, Benjamin J.E

    Molecular cell. 2021 May 06, v. 81, no. 9

    2021  

    Abstract: Recent work from Zhu et al. (2021) reveals that extrachromosomal DNA circles harboring enhancers can serve as mobile regulatory elements that interact with chromosomal oncogenes, stimulating high-level gene activity and contributing to tumor ... ...

    Abstract Recent work from Zhu et al. (2021) reveals that extrachromosomal DNA circles harboring enhancers can serve as mobile regulatory elements that interact with chromosomal oncogenes, stimulating high-level gene activity and contributing to tumor heterogeneity and cancer progression.
    Keywords DNA ; neoplasm progression ; neoplasms ; oncogenes
    Language English
    Dates of publication 2021-0506
    Size p. 1866-1867.
    Publishing place Elsevier Inc.
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2021.04.017
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Screening thousands of transcribed coding and non-coding regions reveals sequence determinants of RNA polymerase II elongation potential.

    Vlaming, Hanneke / Mimoso, Claudia A / Field, Andrew R / Martin, Benjamin J E / Adelman, Karen

    Nature structural & molecular biology

    2022  Volume 29, Issue 6, Page(s) 613–620

    Abstract: Precise regulation of transcription by RNA polymerase II (RNAPII) is critical for organismal growth and development. However, what determines whether an engaged RNAPII will synthesize a full-length transcript or terminate prematurely is poorly understood. ...

    Abstract Precise regulation of transcription by RNA polymerase II (RNAPII) is critical for organismal growth and development. However, what determines whether an engaged RNAPII will synthesize a full-length transcript or terminate prematurely is poorly understood. Notably, RNAPII is far more susceptible to termination when transcribing non-coding RNAs than when synthesizing protein-coding mRNAs, but the mechanisms underlying this are unclear. To investigate the impact of transcribed sequence on elongation potential, we developed a method to screen the effects of thousands of INtegrated Sequences on Expression of RNA and Translation using high-throughput sequencing (INSERT-seq). We found that higher AT content in non-coding RNAs, rather than specific sequence motifs, drives RNAPII termination. Further, we demonstrate that 5' splice sites autonomously stimulate processive transcription, even in the absence of polyadenylation signals. Our results reveal a potent role for the transcribed sequence in dictating gene output and demonstrate the power of INSERT-seq toward illuminating these contributions.
    MeSH term(s) High-Throughput Nucleotide Sequencing ; Polyadenylation ; RNA Polymerase II/genetics ; RNA Polymerase II/metabolism ; RNA, Messenger/metabolism ; Transcription, Genetic
    Chemical Substances RNA, Messenger ; RNA Polymerase II (EC 2.7.7.-)
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/s41594-022-00785-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Global identification of SWI/SNF targets reveals compensation by EP400.

    Martin, Benjamin J E / Ablondi, Eileen F / Goglia, Christine / Mimoso, Claudia A / Espinel-Cabrera, Piero R / Adelman, Karen

    Cell

    2023  Volume 186, Issue 24, Page(s) 5290–5307.e26

    Abstract: Mammalian SWI/SNF chromatin remodeling complexes move and evict nucleosomes at gene promoters and enhancers to modulate DNA access. Although SWI/SNF subunits are commonly mutated in disease, therapeutic options are limited by our inability to predict SWI/ ...

    Abstract Mammalian SWI/SNF chromatin remodeling complexes move and evict nucleosomes at gene promoters and enhancers to modulate DNA access. Although SWI/SNF subunits are commonly mutated in disease, therapeutic options are limited by our inability to predict SWI/SNF gene targets and conflicting studies on functional significance. Here, we leverage a fast-acting inhibitor of SWI/SNF remodeling to elucidate direct targets and effects of SWI/SNF. Blocking SWI/SNF activity causes a rapid and global loss of chromatin accessibility and transcription. Whereas repression persists at most enhancers, we uncover a compensatory role for the EP400/TIP60 remodeler, which reestablishes accessibility at most promoters during prolonged loss of SWI/SNF. Indeed, we observe synthetic lethality between EP400 and SWI/SNF in cancer cell lines and human cancer patient data. Our data define a set of molecular genomic features that accurately predict gene sensitivity to SWI/SNF inhibition in diverse cancer cell lines, thereby improving the therapeutic potential of SWI/SNF inhibitors.
    MeSH term(s) Animals ; Humans ; Chromatin ; Chromatin Assembly and Disassembly ; Nuclear Proteins/metabolism ; Nucleosomes ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Mice
    Chemical Substances Chromatin ; Nuclear Proteins ; Nucleosomes ; Transcription Factors ; Ep400 protein, mouse (EC 3.6.4.-)
    Language English
    Publishing date 2023-11-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2023.10.006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS and AML.

    Wheeler, Emily C / Martin, Benjamin J E / Doyle, William C / Neaher, Sofia / Conway, Caroline A / Pitton, Caroline N / Gorelov, Rebecca A / Donahue, Melanie / Jann, Johann C / Abdel-Wahab, Omar / Taylor, Justin / Seiler, Michael / Buonamici, Silvia / Pikman, Yana / Garcia, Jacqueline S / Belizaire, Roger / Adelman, Karen / Tothova, Zuzana

    Science translational medicine

    2024  Volume 16, Issue 728, Page(s) eade2774

    Abstract: Splicing modulation is a promising treatment strategy pursued to date only in splicing factor-mutant cancers; however, its therapeutic potential is poorly understood outside of this context. Like splicing factors, genes encoding components of the cohesin ...

    Abstract Splicing modulation is a promising treatment strategy pursued to date only in splicing factor-mutant cancers; however, its therapeutic potential is poorly understood outside of this context. Like splicing factors, genes encoding components of the cohesin complex are frequently mutated in cancer, including myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML), where they are associated with poor outcomes. Here, we showed that cohesin mutations are biomarkers of sensitivity to drugs targeting the splicing factor 3B subunit 1 (SF3B1) H3B-8800 and E-7107. We identified drug-induced alterations in splicing, and corresponding reduced gene expression, of a number of DNA repair genes, including
    MeSH term(s) Humans ; Cohesins ; Myelodysplastic Syndromes/drug therapy ; Myelodysplastic Syndromes/genetics ; Myelodysplastic Syndromes/metabolism ; RNA Splicing ; RNA Splicing Factors/genetics ; Mutation/genetics ; Transcription Factors/metabolism ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; DNA Repair/genetics ; Phosphoproteins/genetics ; Phosphoproteins/metabolism ; DNA Damage
    Chemical Substances Cohesins ; RNA Splicing Factors ; Transcription Factors ; Phosphoproteins
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.ade2774
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Transcription Promotes the Interaction of the FAcilitates Chromatin Transactions (FACT) Complex with Nucleosomes in

    Martin, Benjamin J E / Chruscicki, Adam T / Howe, LeAnn J

    Genetics

    2018  Volume 210, Issue 3, Page(s) 869–881

    Abstract: The FACT (FAcilitates Chromatin Transactions) complex is a conserved complex that maintains chromatin structure on transcriptionally active genes. Consistent with this, FACT is enriched on highly expressed genes, but how it is targeted to these regions ... ...

    Abstract The FACT (FAcilitates Chromatin Transactions) complex is a conserved complex that maintains chromatin structure on transcriptionally active genes. Consistent with this, FACT is enriched on highly expressed genes, but how it is targeted to these regions is unknown.
    MeSH term(s) DNA-Binding Proteins/metabolism ; DNA-Directed RNA Polymerases/metabolism ; High Mobility Group Proteins/metabolism ; Nucleosomes/metabolism ; Protein Binding ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Transcription, Genetic/genetics ; Transcriptional Elongation Factors/metabolism
    Chemical Substances DNA-Binding Proteins ; FACT protein, S cerevisiae ; High Mobility Group Proteins ; Nucleosomes ; Saccharomyces cerevisiae Proteins ; Transcriptional Elongation Factors ; DNA-Directed RNA Polymerases (EC 2.7.7.6)
    Language English
    Publishing date 2018-09-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2167-2
    ISSN 1943-2631 ; 0016-6731
    ISSN (online) 1943-2631
    ISSN 0016-6731
    DOI 10.1534/genetics.118.301349
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Transcription shapes genome-wide histone acetylation patterns.

    Martin, Benjamin J E / Brind'Amour, Julie / Kuzmin, Anastasia / Jensen, Kristoffer N / Liu, Zhen Cheng / Lorincz, Matthew / Howe, LeAnn J

    Nature communications

    2021  Volume 12, Issue 1, Page(s) 210

    Abstract: Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. ... ...

    Abstract Histone acetylation is a ubiquitous hallmark of transcription, but whether the link between histone acetylation and transcription is causal or consequential has not been addressed. Using immunoblot and chromatin immunoprecipitation-sequencing in S. cerevisiae, here we show that the majority of histone acetylation is dependent on transcription. This dependency is partially explained by the requirement of RNA polymerase II (RNAPII) for the interaction of H4 histone acetyltransferases (HATs) with gene bodies. Our data also confirms the targeting of HATs by transcription activators, but interestingly, promoter-bound HATs are unable to acetylate histones in the absence of transcription. Indeed, HAT occupancy alone poorly predicts histone acetylation genome-wide, suggesting that HAT activity is regulated post-recruitment. Consistent with this, we show that histone acetylation increases at nucleosomes predicted to stall RNAPII, supporting the hypothesis that this modification is dependent on nucleosome disruption during transcription. Collectively, these data show that histone acetylation is a consequence of RNAPII promoting both the recruitment and activity of histone acetyltransferases.
    MeSH term(s) Acetylation ; Animals ; Chromatin/metabolism ; Genome, Fungal ; Histone Acetyltransferases/metabolism ; Histones/metabolism ; Mice ; Saccharomyces cerevisiae/genetics ; Trans-Activators/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; Histones ; Trans-Activators ; Histone Acetyltransferases (EC 2.3.1.48)
    Language English
    Publishing date 2021-01-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-20543-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Strength is in engagement: The rise of an online scientific community during the COVID-19 pandemic.

    Cucinotta, Christine E / Martin, Benjamin J E / Noé González, Melvin / Raman, Pravrutha / Teif, Vladimir B / Vlaming, Hanneke

    EMBO reports

    2021  Volume 22, Issue 5, Page(s) e52612

    Abstract: Many scientists, confined to home office by COVID-19, have been gathering in online communities, which could become viable alternatives to physical meetings and conferences. ...

    Abstract Many scientists, confined to home office by COVID-19, have been gathering in online communities, which could become viable alternatives to physical meetings and conferences.
    MeSH term(s) COVID-19 ; Humans ; Pandemics ; SARS-CoV-2
    Language English
    Publishing date 2021-05-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.202152612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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