Although numerous studies have underlined the role of histone deacetylases (HDAC) in breast physiology and tumorigenesis, little is known on the particular contribution of the various classes of HDACs in these processes. Using estrogen receptor-A (ERA) -positive MCF-7 breast cancer cells, the effects of MC1575 and MC1568, two novel class II -specific HDAC inhibitors, were analyzed on cell proliferation, apoptosis, and estrogen signaling. The specificity of these HDAC inhibitors was validated by measuring histone and A-tubulin acetylation and by the specific in vitro inhibition of recombinant HDAC4 using histone and nonhistone substrates, contrasting with the lack of inhibition of class I HDACs. In addition, MC1575 did not inhibit class I HDAC gene expression, thus confirming the specific targeting of class II enzymes. Similar to trichostatin A (TSA), MC1575 displayed a dosedependent antiproliferative effect and induced cell cycle arrest although this blockade occurred at a different level than TSA. Moreover, and in contrast to TSA,
Background Containment, involving separation and restriction of movement of people due to the COVID-19 pandemic, and mitigation, also referred to as lockdown, involving closure of schools, universities and public venues, has had a profound impact on people’s lives globally. The study focuses on the effects of containment and mitigation measures, on the behavior of children and youth (CaY) with Autism Spectrum Disorders (ASD). The study primary aim was to examine the impact of these urgent measures on the behaviors, communication, sleep, and nutritional status of the CaY. A secondary aim was to explore risk and protective factors on behavior change including sociodemographic variables, living conditions, ASD symptom severity and continuity of interventions. Methods The study sample consisted of 239 ASD subjects, 2 to 21 years of age, enrolled in the ELENA cohort in France at Stage 3 confinement and mitigation measures announced on March 16, 2020. A parent informant completed the COVID-19 questionnaire. Results Of the domains examined, challenging behaviors, communicative skills and sleep had the greatest impact; in terms of risk and protective factors, subject age, ASD severity, single parenthood, daily living skills, and intervention continuity were most likely to impact behaviors; living conditions were not linked to behavior change. Conclusions The findings highlight the topography of behavioral change in CaY with ASD following institution of containment and mitigation measures during the COVID-19 pandemic and help identify risk and protective factors to help better address needs and tailor interventions in the future.
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