Activation of diacylglycerol kinase alpha is required for VEGF-induced angiogenic signaling in vitro.

Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis by stimulating migration, proliferation and organization of endothelium, through the activation of signaling pathways involving Src tyrosine kinase. As we had previously shown that Src-mediated activation of diacylglycerol kinase-alpha (Dgk-alpha) is required for hepatocytes growth factor-stimulated cell migration, we asked whether Dgk-alpha is involved in the transduction of angiogenic signaling. In PAE-KDR cells, an endothelial-derived cell line expressing VEGFR-2, VEGF-A165, stimulates the enzymatic activity of Dgk-alpha: activation is inhibited by R59949, an isoform-specific Dgk inhibitor, and is dependent on Src tyrosine kinase, with which Dgk-alpha forms a complex. Conversely in HUVEC, VEGF-A165-induced activation of Dgk is only partially sensitive to R59949, suggesting that also other isoforms may be activated, albeit still dependent on Src tyrosine kinase. Specific inhibition of Dgk-alpha, obtained in both cells by R59949 and in PAE-KDR by expression of Dgk-alpha dominant-negative mutant, impairs VEGF-A165-dependent chemotaxis, proliferation and in vitro angiogenesis. In addition, in HUVEC, specific downregulation of Dgk-alpha by siRNA impairs in vitro angiogenesis on matrigel, further suggesting the requirement for Dgk-alpha in angiogenic signaling in HUVEC. Thus, we propose that activation of Dgk-alpha generates a signal essential for both proliferative and migratory response to VEGF-A165, suggesting that it may constitute a novel pharmacological target for angiogenesis control.

Piattaforme digitali: tra criticità concorrenziali e prospettive di regolamentazione

È indubbio che le piattaforme digitali abbiano oggi un impatto tale da condizionare in maniera trasversale tutti gli aspetti delle relazioni umane, personali ed economiche, così rendendo le predette piattaforme dei veri e propri giganti della nostra società, attraverso i quali si rapportano quotidianamente miliardi di persone, eleggendo i social network quale luogo digitale di incontro, le piattaforme di e-commerce a nuovi mercati, i motori di ricerca a porte sullo scibile umano. In tale contesto, è sorto però il dibattito circa la necessità di una regolamentazione unitaria e teleologicamente orientata del fenomeno delle piattaforme digitali. Invero, da più parti è stato sollevato il dubbio che l’inarrestabile sviluppo delle piattaforme digitali sia proprio dovuto alla mancanza di un quadro regolamentare in grado di porre freno ai comportamenti opportunistici di questi nuovi giganti digitali. Su tali premesse, scopo della presente trattazione sarà quello di andare ad analizzare le problematiche concorrenziali che caratterizzano i mercati animati dalle piattaforme digitali. Ciò al fine di verificare se gli strumenti e gli schemi del diritto antitrust siano in grado di rispondere alle sfide concorrenziali poste dalle piattaforme digitali o se, viceversa, sia necessario approntare un quadro regolamentare ad hoc. Pertanto, nella prima parte della trattazione si cercherà di connotare il concetto di piattaforma digitale, in modo da individuare i contorni di una nozione all'apparenza, e nella sostanza, complessa. Nella seconda parte verrà esaminata la possibilità di adoperare gli strumenti generalmente utilizzati per la definizione del mercato rilevante anche in contesti fluidi come quelli in cui operano le piattaforme in questione. Nella terza e nella quarta parte si esamineranno le sfide che i mercati della new economy pongono agli operatori del diritto antitrust, rispettivamente nell’applicazione del divieto di intese anticoncorrenziali, di cui all’art. 101 del Trattato sul Funzionamento dell’Unione europea (di seguito “TFUE”) e dell’abuso di posizione dominante, ai sensi dell’art. 102 TFUE. L’ultimo parte della trattazione sarà invece dedicata ad esaminare le problematiche concorrenziali scaturenti dalle operazioni di concentrazione che coinvolgono le piattaforme digitali

A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function.

We report on a homozygous frameshift deletion in DDX59 (c.185del: p.Phe62fs*13) in a family presenting with orofaciodigital syndrome phenotype associated with a broad neurological involvement characterized by microcephaly, intellectual disability, epilepsy, and white matter signal abnormalities associated with cortical and subcortical ischemic events. DDX59 encodes a DEAD-box RNA helicase and its role in brain function and neurological diseases is unclear. We showed a reduction of mutant cDNA and perturbation of SHH signaling from patient-derived cell lines; furthermore, analysis of human brain gene expression provides evidence that DDX59 is enriched in oligodendrocytes and might act within pathways of leukoencephalopathies-associated genes. We also characterized the neuronal phenotype of the Drosophila model using mutant mahe, the homolog of human DDX59, and showed that mahe loss-of-function mutant embryos exhibit impaired development of peripheral and central nervous system. Taken together, our results support a conserved role of this DEAD-box RNA helicase in neurological function

Draw a Software Engineer Test -An Investigation into Children’s Perception of Software Engineering Profession

Context: The gender gap is particularly affecting the software engineering community, as both academia and industry are dominated by men. Literature reports how the lack of women is a consequence of gender stereotypes around certain figures that begin in the early stages of education, affecting children’s perceptions of the role they can play across scientific fields.Objective: In this study, we asked children to draw a software engineer in order to collect their perceptions and let us check whether gender stereotypes still persist.Methods: We asked a total of 371 children to draw a person who works in the software engineering field. We analyzed the drawings based on a set of parameters extracted from literature and inspected the results through a cross-sectional study.Results: Children agreed on their representations of a software engineer: 51% drew a man and 44% drew a woman, while 5% a non-recognizable figure. The main differences emerged when the data were grouped by age and gender: only 23% of eleven-year-old girls drew a woman software engineer, while 54% drew a man, and in 23% gender was non-recognizable.Conclusion: The findings revealed a favorable gender balance in children’s perceptions of software engineering. They seem more willing to recognize diversity, an improvement compared with what was reported in previous studies. Children’s perceptions of technology may have become more accessible as a result of the COVID-19 situation. These findings may draw positive comparisons with the current gender gap in software engineering, encouraging future developments.publishedVersio

The Estrogen Receptor α Signaling Pathway Controls Alternative Splicing in the Absence of Ligands in Breast Cancer Cells.

BACKGROUND: The transcriptional activity of estrogen receptor α (ERα) in breast cancer (BC) is extensively characterized. Our group has previously shown that ERα controls the expression of a number of genes in its unliganded form (apoERα), among which a large group of RNA-binding proteins (RBPs) encode genes, suggesting its role in the control of co- and post-transcriptional events. METHODS: apoERα-mediated RNA processing events were characterized by the analysis of transcript usage and alternative splicing changes in an RNA-sequencing dataset from MCF-7 cells after siRNA-induced ERα downregulation. RESULTS: ApoERα depletion induced an expression change of 681 RBPs, including 84 splicing factors involved in translation, ribonucleoprotein complex assembly, and 3'end processing. ApoERα depletion results in 758 isoform switching events with effects on 3'end length and the splicing of alternative cassette exons. The functional enrichment of these events shows that post-transcriptional regulation is part of the mechanisms by which apoERα controls epithelial-to-mesenchymal transition and BC cell proliferation. In primary BCs, the inclusion levels of the experimentally identified alternatively spliced exons are associated with overall and disease-free survival. CONCLUSION: Our data supports the role of apoERα in maintaining the luminal phenotype of BC cells by extensively regulating gene expression at the alternative splicing level