The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling

The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing $\textit{Drosophila}$eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, $\textit{Drosophila}$ Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways.T.M. and F.M. were partly supported by a CRUK Fellowship to Y.K. T.M. thanks the European Commission for a Marie Curie fellowship

ARIADNE: A Research Infrastructure for Archaeology

Research e-infrastructures, digital archives, and data services have become important pillars of scientific enterprise that in recent decades have become ever more collaborative, distributed, and data intensive. The archaeological research community has been an early adopter of digital tools for data acquisition, organization, analysis, and presentation of research results of individual projects. However, the provision of e-infrastructure and services for data sharing, discovery, access, and (re)use have lagged behind. This situation is being addressed by ARIADNE, the Advanced Research Infrastructure for Archaeological Dataset Networking in Europe. This EU-funded network has developed an e-infrastructure that enables data providers to register and provide access to their resources (datasets, collections) through the ARIADNE data portal, facilitating discovery, access, and other services across the integrated resources. This article describes the current landscape of data repositories and services for archaeologists in Europe, and the issues that make interoperability between them difficult to realize. The results of the ARIADNE surveys on users’ expectations and requirements are also presented. The main section of the article describes the architecture of the e-infrastructure, core services (data registration, discovery, and access), and various other extant or experimental services. The ongoing evaluation of the data integration and services is also discussed. Finally, the article summarizes lessons learned and outlines the prospects for the wider engagement of the archaeological research community in the sharing of data through ARIADNE

From fuzzy to annotated semantic web languages

The aim of this chapter is to present a detailed, selfcontained and comprehensive account of the state of the art in representing and reasoning with fuzzy knowledge in Semantic Web Languages such as triple languages RDF/RDFS, conceptual languages of the OWL 2 family and rule languages. We further show how one may generalise them to so-called annotation domains, that cover also e.g. temporal and provenance extensions

Digital Libraries and Archives

This book constitutes the thoroughly refereed proceedings of the 7th Italian Research Conference on Digital Libraries held in Pisa, Italy, in January 2011. The 20 revised full papers presented were carefully reviewed and cover topics of interest such as system interoperability and data integration; formal and methodological foundations of digital libraries; semantic web and linked data for digital libraries; multilingual information access; digital library infrastructures; metadata creation and management; search engines for digital library systems; evaluation and log data; handling audio/visual and non-traditional objects; user interfaces and visualization; digital library quality

Regulation of regulators: Tbx5 impacts cardiac expression through miR-218 modulation in zebrafish

Background: Tbx5, a member of the T-box gene family, is one of the key transcription factor of vertebrate heart development Minor alterations in its dosage cause Holt-Oram syndrome (HOS) an autosomal dominant disease characterized upper limb malformation and congenital heart defects of variable severity. In mouse model of HOS gene expression profiling revealed that TBX5 regulate a complextranscriptional network probably acting directely on gene expression or indirectely by " regulating regulators" such as TF and miRNAs. The integration of miRNAs and TFs into the genetic cardiac circuitry provides a rich and robust array of regulatory interactions to control cardiac gene expression. Looking for TBX5/miRNA regulatory circuit we identified miR-218 which, together with its host gene, Slit2, has been already shown to be involved in heart development. Purpose: the goal of our project is to demonstrate the existence of a regulatory circuit involving Tbx5/slit2/miR-218 and its importance in cardiac development. Methods: For in vitro studies P19CL6, a murine cell line able to differentiate cardiomyocites were utilized. For in vivo functional studies, gain and loss of function experiments of both, Tbx5 and Results: in cardiomyocyte differentiation of mouse P19CL6 cell culture, we confirmed a correlation between Tbx5 and miR-218 expression. Using zebrafish model, we showed that alterations of miR-218 expression have a deep impact on heart development. Interestingly, down-regulation of miR-218 was able to almost rescue defects generated by Tbx5 over-expression, confirming a functional relation between these two regulators. Conclusions: these data demonstrate that TBX5 directly and indirectly controls TF/miRNA regulatory circuitries and support the importance of miRNA regulationin HOS

Logical and computational properties of the description logic MIRTL

In recent years a number of positive (i.e. tractability and decidability) results have been found concerning the computational complexity of Description Logics (DLs) [Buchheit et al.,1993; Donini et al.,1991

Deep learning for decentralized parking lot occupancy detection

A smart camera is a vision system capable of extracting application-specific information from the captured images. The paper proposes a decentralized and efficient solution for visual parking lot occupancy detection based on a deep Convolutional Neural Network (CNN) specifically designed for smart cameras. This solution is compared with state-of-the-art approaches using two visual datasets: PKLot, already existing in literature, and CNRPark-EXT. The former is an existing dataset, that allowed us to exhaustively compare with previous works. The latter dataset has been created in the context of this research, accumulating data across various seasons of the year, to test our approach in particularly challenging situations, exhibiting occlusions, and diverse and difficult viewpoints. This dataset is public available to the scientific community and is another contribution of our research. Our experiments show that our solution outperforms and generalizes the best performing approaches on both datasets. The performance of our proposed CNN architecture on the parking lot occupancy detection task, is comparable to the well-known AlexNet, which is three orders of magnitude larger

The programmed destabilisation of centrioles in the Drosophila egg chamber through the APC/C ubiquitination pathway

Resumen del póster presentado a la 25th European Drosophila Research Conference, celebrada en Londres (UK) del 22 al 25 de septiembre de 2017.Centrioles are organelles that are present in most of animal cells and are often part of a larger complex called the centrosome, which is composed of the centrioles and pericentriolar material (PCM). The centrosomes regulate various cellular processes, including cell division and establishing cell polarity through their microtubule organising capabilities. In particular, centrosomes are necessary for ciliogenesis and asymmetric cell divisions. In the Drosophila melanogaster egg chamber centriole elimination is thought to prevent parthenogenesis, due to a reticulate mechanism of egg activation prior to fertilisation. lf the centrioles are not eliminated during Drosophila female germline development then the eggs are sterile. However, the centrioles of the germline not only have to be eliminated, but must undergo a peculiar orchestrated relocalisation to the oocyte prior to this elimination. Therefore, centrioles must be strictly controlled for Drosophila fertility. Despite the importance of centriole maintenance in the female germline, the mechanism of this germline-specific regulation is still nebulous. With a modified version of the anaphase promoting complex/cyclosome (APC/C), we show that precise control of the APC/C is responsible for centriole/centrosome regulation during Drosophila oogenesis. The APC/C regulates the programmed destruction of various cell cycle proteins, and we show that in the female germline this includes Polo, a key regulator necessary for PCM and thus centriole stability. lt is through the specifically timed destruction of Polo that the APC/C enables germline centriole elimination. In addition to this, we show the developmental consequence of ectopic centriole regulation.Peer Reviewe