Experience without Sight: The Opportunity for Reflection of Normative Space

Osman, Robert; Pospíšilová, Lucie

doi:10.13060/12130028.2016.17.1.256

Cited by 6 publications

(2 citation statements)

References 37 publications

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“…3A). In good concert with this, pharmacological inhibition of RUNX1-ETO by two calpain inhibitors MG-101 and MDL-28170 (59,60) signi cantly downregulated BCAT1 expression (Fig. 3B, Supplemental Fig.…”

Section: Runx1-eto Directly Activates Bcat1 Via a Runx1-dependent Mannermentioning

confidence: 75%

RUNX1-ETO and CBFβ-MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core binding factor-acute myeloid leukemia

Wang

Liu

Zhao

et al. 2023

Preprint

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Background: Effective targeted therapy is an unmet clinical need for core binding factor-acute myeloid leukemia (CBF-AML) characterized by RUNX1-ETO and CBFb-MYH11 fusions. However, therapeutically targeting oncogenic fusions involving transcription factors remains challenging. Recent studies point to aberrant amino acid metabolisms as actionable therapeutic targets. Methods: We analyzed the expression of BCAT1in a large cohort of AML patients and a series of AML cell lines. Altered BCAA metabolism was assessed by metabolic profiling. Transcriptional activation of BCAT1by RUNX1-ETO and CBFb-MYH11 fusions was determined by ChIP-seq data, luciferase reporter assays, genetic manipulation, and chromatin conformation analysis. Anti-leukemic effects of inhibiting BCAT1 by genetic and pharmaceutical approaches were evaluated both in vitro and in vivo. Results: High expression of BCAT1was exclusively found in CBF-AML patients and subsequently led to reprogrammed BCAA metabolism. Mechanistically, RUNX1-ETO and CBFb-MYH11 fusion proteins bound to chromatin to activate BCAT1 expression in a similar wild-type RUNX1-dependent manner through rewiring the chromatin conformation at the BCAT1gene locus. Functionally, BCAT1 inhibition resulted in blunted cell cycle, enhanced apoptosis, and myeloid differentiation of CBF-AML cells in vitro, pointing to critical dependence on BCAA metabolism. Strikingly, in vivotherapeutic effects of inhibiting BCAT1 by its specific inhibitor, Gabapentin, were evidenced by delayed leukemia progression and improved survival using the xenografted mouse model. Conclusions: RUNX1-ETO and CBFβ-MYH11 converge on aberrant activation of BCAT1, representing a targeted therapeutic opportunity for CBF-AML.

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Section: Runx1-eto Directly Activates Bcat1 Via a Runx1-dependent Mannermentioning

confidence: 75%

RUNX1-ETO and CBFβ-MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core binding factor-acute myeloid leukemia

Wang

Liu

Zhao

et al. 2023

Preprint

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show abstract

“…He also learnt chic colour combinations and has a favourite clothes shop with nice shop assistants who always give him good advice, so people praise his look. This mandatory compliance with the visual world is often criticized (Michalko, 1999;Osman & Pospíšilová, 2016), but my point goes elsewhere -not even colours are purely visual.…”

Section: Authormentioning

confidence: 97%

Revising modern divisions between blindness and sightedness: Doing knowledge in blind assemblages

Porkertová

2022

The Sociological Review

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Western society associates knowledge with vision while affiliating blindness with ignorance. Following critical disability studies and drawing upon non-structured interview data and ethnographic observations with visually disabled people, the article opposes this idea by examining how blind assemblages construct knowledge and highlight its heterogeneous and dynamic character, usually obscured by visual shortcuts. After discussing how the research participants encounter discourses devaluating knowledge not based primarily on vision, the article focuses on divisive practices that lead to the construction of dis/ability and ab/normality, and how they can be revised by conceiving knowledge, senses and dis/ability as assemblages. The heterogeneous and dynamic character of knowledge, which the text argues for, defies perceiving blindness as a deficit and blurs the divisions between the self and the other as well as the sighted and the blind since knowledge is produced collectively.

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“Almost Equal”: Confronting Norms and Normality in Experiencing Visual Disability

Porkertová

2020

Critical Sociology

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This article examines the everyday experience of visually disabled people with norms and normality and confronts it with three approaches discussed in disability studies: (i) the medical model, (ii) the social model, and (iii) critical disability studies. The most available model to the people in the study, as well as the most widespread approach in Czech society, is the medical model. However, the text shows that although other approaches are rather marginal, their logic is present in the everyday experience of the communication partners in the research. They can espouse the rigid, medical model, while, at the same time, confronting the construction of norms that both the social model and critical disability studies defy. This finding reveals both the normative and subversive character of disability, manifested in visually impaired experience.

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Experience without Sight: The Opportunity for Reflection of Normative Space

Cited by 6 publications

References 37 publications

RUNX1-ETO and CBFβ-MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core binding factor-acute myeloid leukemia

RUNX1-ETO and CBFβ-MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core binding factor-acute myeloid leukemia

Revising modern divisions between blindness and sightedness: Doing knowledge in blind assemblages

“Almost Equal”: Confronting Norms and Normality in Experiencing Visual Disability

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