Diagnosis of learning difficulties of plate tectonics concepts among secondary school students using: Focus group, nominal group, and questionnaire

The teaching of geology or earth sciences occupies an important place in the life and earth sciences programs of the secondary cycle in Morocco. The theory of plate tectonics is the conceptual model that allows an understanding of most of the dynamic processes of the Earth. Our work aims to diagnose the difficulties related to the learning of the concepts related to plate tectonics by following a hybrid methodology of three techniques, namely: focus group, nominal group, and questionnaire. The results obtained allowed us to identify difficulties in the educational act in its different facets, whether epistemological, pedagogical, didactic, curricular, and logistical. These difficulties should be taken into consideration by the different actors in the educational process, in order to guarantee the successful learning of this discipline

Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines

Direct modulation of gene expression by targeting oncogenic transcription factors is a new area of research for cancer treatment. ERG, an ETS-family transcription factor, is commonly over-expressed or translocated in leukaemia and prostate carcinoma. In this work, we selected the di-(thiophene-phenylamidine) compound DB1255 as an ERG/DNA binding inhibitor using a screening test of synthetic inhibitors of the ERG/DNA interaction followed by electrophoretic mobility shift assays (EMSA) validation. Spectrometry, footprint and biosensor-surface plasmon resonance analyses of the DB1255/DNA interaction evidenced sequence selectivity and groove binding as dimer. Additional EMSA evidenced the precise DNA-binding sequence required for optimal DB1255/DNA binding and thus for an efficient ERG/DNA complex inhibition. We further highlighted the structure activity relationshipsfrom comparison with derivatives. In cellulo luciferase assay confirmed this modulation both with the constructed optimal sequences and the Osteopontin promoter known to be regulated by ERG and which ERG-binding site was protected from DNaseI digestion on binding of DB1255. These data showed for the first time the ERG/DNA complex modulation, both in vitro and in cells, by a heterocyclic diamidine that specifically targets a portion of the ERG DNA recognition site

Recent advances in the structural molecular biology of Ets transcription factors: interactions, interfaces and inhibition

The Ets family of eukaryotic transcription factors is based around the conserved Ets DNA-binding domain. Although their DNA-binding selectivity is biochemically and structurally well characterized, structures of homodimeric and ternary complexes point to Ets domains functioning as versatile protein-interaction modules. In the present paper, we review the progress made over the last decade to elucidate the structural mechanisms involved in modulation of DNA binding and protein partner selection during dimerization. We see that Ets domains, although conserved around a core architecture, have evolved to utilize a variety of interaction surfaces and binding mechanisms, reflecting Ets domains as dynamic interfaces for both DNA and protein interaction. Furthermore, we discuss recent advances in drug development for inhibition of Ets factors, and the roles structural biology can play in their future

Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs

Diagnosis of learning difficulties of plate tectonics concepts among secondary school students using: Focus group, nominal group, and questionnaire

The teaching of geology or earth sciences occupies an important place in the life and earth sciences programs of the secondary cycle in Morocco. The theory of plate tectonics is the conceptual model that allows an understanding of most of the dynamic processes of the Earth. Our work aims to diagnose the difficulties related to the learning of the concepts related to plate tectonics by following a hybrid methodology of three techniques, namely: focus group, nominal group, and questionnaire. The results obtained allowed us to identify difficulties in the educational act in its different facets, whether epistemological, pedagogical, didactic, curricular, and logistical. These difficulties should be taken into consideration by the different actors in the educational process, in order to guarantee the successful learning of this discipline