Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division

Proliferation of mammalian cells requires the coordinated function of many proteins to accurately divide a cell into two daughter cells. Several RNAi screens have identified previously uncharacterised genes that are implicated in mammalian cell division. The molecular function for these genes needs to be investigated to place them into pathways. Phenotypic profiling is a useful method to assign putative functions to uncharacterised genes. Here, we show that the analysis of protein localisation is useful to refine a phenotypic profile. We show the utility of this approach by defining a function of the previously uncharacterised gene C13orf3 during cell division. C13orf3 localises to centrosomes, the mitotic spindle, kinetochores, spindle midzone, and the cleavage furrow during cell division and is specifically phosphorylated during mitosis. Furthermore, C13orf3 is required for centrosome integrity and anaphase onset. Depletion by RNAi leads to mitotic arrest in metaphase with an activation of the spindle assembly checkpoint and loss of sister chromatid cohesion. Proteomic analyses identify C13orf3 (Ska3) as a new component of the Ska complex and show a direct interaction with a regulatory subunit of the protein phosphatase PP2A. All together, these data identify C13orf3 as an important factor for metaphase to anaphase progression and highlight the potential of combined RNAi screening and protein localisation analyses

Indications for Digital Monitoring of Patients With Multiple Nevi: Recommendations from the International Dermoscopy Society

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring.  Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice

Clinical and dermoscopic characteristics of congenital and non-congenital nevus-associated melanomas

No specific features of nevus-associated melanoma (NAM) are currently defined

Seven non-melanoma features to rule out facial melanoma

Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface) of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p < 0.001). Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8%) and seborrhoeic keratosis (74.3%) and lower for actinic keratosis (61.4%) and lichenoid keratosis (25.6%). Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features

PhenoFam-gene set enrichment analysis through protein structural information

<p>Abstract</p> <p>Background</p> <p>With the current technological advances in high-throughput biology, the necessity to develop tools that help to analyse the massive amount of data being generated is evident. A powerful method of inspecting large-scale data sets is gene set enrichment analysis (GSEA) and investigation of protein structural features can guide determining the function of individual genes. However, a convenient tool that combines these two features to aid in high-throughput data analysis has not been developed yet. In order to fill this niche, we developed the user-friendly, web-based application, PhenoFam.</p> <p>Results</p> <p>PhenoFam performs gene set enrichment analysis by employing structural and functional information on families of protein domains as annotation terms. Our tool is designed to analyse complete sets of results from quantitative high-throughput studies (gene expression microarrays, functional RNAi screens, <it>etc</it>.) without prior pre-filtering or hits-selection steps. PhenoFam utilizes Ensembl databases to link a list of user-provided identifiers with protein features from the InterPro database, and assesses whether results associated with individual domains differ significantly from the overall population. To demonstrate the utility of PhenoFam we analysed a genome-wide RNA interference screen and discovered a novel function of plexins containing the cytoplasmic RasGAP domain. Furthermore, a PhenoFam analysis of breast cancer gene expression profiles revealed a link between breast carcinoma and altered expression of PX domain containing proteins.</p> <p>Conclusions</p> <p>PhenoFam provides a user-friendly, easily accessible web interface to perform GSEA based on high-throughput data sets and structural-functional protein information, and therefore aids in functional annotation of genes.</p

A Genome-Scale DNA Repair RNAi Screen Identifies SPG48 as a Novel Gene Associated with Hereditary Spastic Paraplegia

We have identified a novel gene in a genome-wide, double-strand break DNA repair RNAi screen and show that is involved in the neurological disease hereditary spastic paraplegia

Living Differently, Seeing Differently : Carla Accardi's temporary structures (1965-1972)

This article takes as its focus a small group of transparent temporary shelters made by Rome-based artist Carla Accardi between 1965 and 1972. Described by the artist as 'the simplest idea of home', these temporary dwellings are made using Sicofoil, an industrially produced plastic material. Accardi has consistently spoken about these environments in terms of offering another way of living. As such these works resonate with the larger tendency of this period to look to other social models and forms of existence. They bear obvious affinities with the emerging discourse on nomadism, the legacy of Buckminster Fuller's dome culture, the anti-modernist rhetoric of the International Movement for an Imagist Bauhaus, and the inflatable, lightweight, and adaptable structures that animate so much of 1960s architectural practice. In this context, Accardi's Tenda (1965) has even been described as a prototype for many of the temporary structures made by artists associated with Arte Povera throughout the 1960s. Moreover, for Accardi, this signalled a key turning point in her practice at a moment when she had wanted to transform the experience of making and viewing art. The implications of Accardi's use of Sicofoil are examined here to ask how the artist's proposal for an alternative way of living could be premised on a way of seeing differently and how in turn this might be made to speak to feminist concerns with which Accardi was involved as founding member of La Rivolta Femminile. Specifically, Kittler explores in what ways Accardi's continued commitment to art could speak to a utopian possibility for feminism

Bruno Munari versus Programmed Art: A Contradictory Situation, 1961-1967

In May 1962, the Olivetti showroom in the Galleria Vittorio Emanuele in Milan hosted the exhibition Arte programmata. Arte cinetica. OPere moltiplicate. Opera aperta, organized by Bruno Munari and Giorgio Soavi. On show, in addition to pieces by Munari himself, were works by Enzo Mari, the Italian Gruppo T and Gruppo N. Munari's collaboration with Olivetti over Programmed Art was relatively brief: yet, n the space of only five years, the artists associated with it found success and popularity not only in Italy but also in Europe more broadly and in the US. While the success of Munari's collaboration had enabled the artists involved in Programmed Art to develop a new conceptual and visual vocabulary, Munari's final assessment of it was sceptical. This chapter aims to interlink several moments between 1961 and 1967 in the course of which the original idea of Programmed Art came to be progressively modified, if not radically transfigured when the success of Programmed Art on the European and American markets became increasingly irreconcilable with the original purposes Munari had conceived for it