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3. Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzi histone deacetylase DAC2

Author

Marek, Martin, primary, Ramos-Morales, Elizabeth, additional, Picchi-Constante, Gisele F.A., additional, Bayer, Theresa, additional, Norström, Carina, additional, Herp, Daniel, additional, Sales-Junior, Policarpo A., additional, Guerra-Slompo, Eloise P., additional, Hausmann, Kristin, additional, Chakrabarti, Alokta, additional, Shaik, Tajith B., additional, Merz, Annika, additional, Troesch, Edouard, additional, Schmidtkunz, Karin, additional, Goldenberg, Samuel, additional, Pierce, Raymond J., additional, Mourão, Marina M., additional, Jung, Manfred, additional, Schultz, Johan, additional, Sippl, Wolfgang, additional, Zanchin, Nilson I.T., additional, and Romier, Christophe, additional

Published
2021
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6. Identifying Less Accurately Measured Students.

Author

Moen, Ross, Liu, Kristi, Thurlow, Martha, Lekwa, Adam, Scullin, Sarah, and Hausmann, Kristin

Subjects
READING Skills Competency Tests, EDUCATIONAL evaluation, TEACHER expectations, TIME on task (Education), TEACHER evaluation, STUDENT activities
Abstract

Some students are less accurately measured by typical reading tests than other students. By asking teachers to identify students whose performance on state reading tests would likely underestimate their reading skills, this study sought to learn about characteristics of less accurately measured students while also evaluating how well teachers can make such judgments. Twenty students identified by eight teachers participated in structured interviews and completed brief assessments matched to characteristics their teachers said impeded the students' test performance. Researchers found information from evidence provided by teachers, teacher and student interviews, and student assessments that confirmed teacher judgments for some students and information that failed to confirm or was at odds with teacher judgments for other students. Along with observations about student characteristics that affect assessment accuracy, recommendations from the study include suggestions for working with teachers who are asked to make judgments about test accuracy and procedures for confirming teacher judgments. [ABSTRACT FROM AUTHOR]

Published
2009

7. Species-selective targeting of pathogens revealed by the atypical structure and active site of Trypanosoma cruzihistone deacetylase DAC2

Author

Marek, Martin, Ramos-Morales, Elizabeth, Picchi-Constante, Gisele F.A., Bayer, Theresa, Norström, Carina, Herp, Daniel, Sales-Junior, Policarpo A., Guerra-Slompo, Eloise P., Hausmann, Kristin, Chakrabarti, Alokta, Shaik, Tajith B., Merz, Annika, Troesch, Edouard, Schmidtkunz, Karin, Goldenberg, Samuel, Pierce, Raymond J., Mourão, Marina M., Jung, Manfred, Schultz, Johan, Sippl, Wolfgang, Zanchin, Nilson I.T., and Romier, Christophe

Abstract

Writing and erasing of posttranslational modifications are crucial to phenotypic plasticity and antigenic variation of eukaryotic pathogens. Targeting pathogens’ modification machineries, thus, represents a valid approach to fighting parasitic diseases. However, identification of parasitic targets and the development of selective anti-parasitic drugs still represent major bottlenecks. Here, we show that the zinc-dependent histone deacetylases (HDACs) of the protozoan parasite Trypanosoma cruziare key regulators that have significantly diverged from their human counterparts. Depletion of T. cruziclass I HDACs tcDAC1 and tcDAC2 compromises cell-cycle progression and division, leading to cell death. Notably, tcDAC2 displays a deacetylase activity essential to the parasite and shows major structural differences with human HDACs. Specifically, tcDAC2 harbors a modular active site with a unique subpocket targeted by inhibitors showing substantial anti-parasitic effects in celluloand in vivo. Thus, the targeting of the many atypical HDACs in pathogens can enable anti-parasitic selective chemical impairment.

Published
2021
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