Olivier-Van Stichelen, S. | bioRxiv Science

bioRxiv2021

EpyNN: Educational python for Neural Networks

SummaryArtificial Neural Networks (ANNs) have achieved unequaled performance for numerous problems in many areas of Science, Business, Public Policy, and more. While experts are familiar with performance-oriented software and underlying theory, ANNs are difficult to comprehend for non-experts because it requires skills in programming, background in mathematics and knowledge of terminology and concepts. In this work, we release EpyNN, an educational python resource meant for a public willing to understand key concepts and practical implementation of scalable ANN architectures from concise, homogeneous and idiomatic source code. EpyNN contains an educational Application Programming Interface (API), educational workflows from data preparation to ANN training and a documentation website setting side-by-side code, mathematics, graphical representation and text to facilitate learning and provide teaching material. Overall, EpyNN provides basics for python-fluent individuals who wish to learn, teach or develop from scratch. AvailabilityEpyNN documentation is available at https://epynn.net and repository can be retrieved from https://github.com/synthaze/epynn. ContactStephanie Olivier-Van-Stichelen, solivier@mcw.edu. Supplementary InformationSupplementary files and listings.

scientific communication and education↗

bioRxiv2021

O-GlcNAcylation is essential for rapid Pomc expression and cell proliferation in corticotropic tumor cells

Pituitary adenomas have a staggering 16.7% lifetime prevalence and can be devastating in many patients due to profound endocrine and neurologic dysfunction. To date, no clear genomic or epigenomic markers correlates with their onset or severity. Herein, we investigate the impact of the O-GlcNAc post-translational modification in their etiology. Found in over 5000 human proteins to date, O-GlcNAcylation dynamically regulates proteins in critical signaling pathways, and its deregulation is involved in cancers progression and endocrine diseases such as diabetes. In this study, we demonstrate that O-GlcNAcylation enzymes were upregulated, particularly in aggressive ACTH-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we show that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hyper-secretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushings disease, materialized by severe endocrine disruption and increased mortality. We demonstrate that Pomc mRNA is stabilized in an O-GlcNAc-dependent manner in response to corticotropic-stimulating hormone (CRH). By impacting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas pathophysiology, including cellular proliferation and hypersecretion.

cell biology↗