Aurora-A expressing tumour cells are deficient for homology-directed DNA double strand-break repair and sensitive to PARP inhibition.

The protein kinase Aurora-A is a major regulator of the cell cycle that orchestrates mitotic entry and is required for the assembly of a functional mitotic spindle. Overexpression of Aurora-A has been strongly linked with oncogenesis and this has led to considerable efforts at therapeutic targeting of the kinase activity of this protein. However, the exact mechanism by which Aurora-A promotes oncogenesis remains unclear. Here, we show that Aurora-A modulates the repair of DNA double-strand breaks (DSBs). Aurora-A expression inhibits RAD51 recruitment to DNA DSBs, decreases DSB repair by homologous recombination and sensitizes cancer cells to PARP inhibition. This impairment of RAD51 function requires inhibition of CHK1 by Polo-like kinase 1 (PLK1). These results identify a novel function of Aurora-A in modulating the response to DNA DSB that likely contributes to carcinogenesis and suggest a novel therapeutic approach to the treatment of cancers overexpressing this protein

Assessing the Performance and Application of Operational Lagrangian Transport HAB Forecasting Systems

Versión del edito

Springtime zooplankton size structure over the continental shelf of the Bay of BiscaY

Linking lower and higher trophic levels requires special focus on the essential role played by mid-trophic levels, i.e., the zooplankton. One of the most relevant pieces of information regarding zooplankton in terms of flux of energy lies in its size structure. In this study, an extensive data set of size measurements is presented, covering parts of the western European continental shelf and slope, from the Galician coast to the Ushant front, during the springs from 2005 to 2012. Zooplankton size spectra were estimated using measurements carried out in situ with the Laser Optical Plankton Counter (LOPC) and with an image analysis of WP2 net samples (200 μm mesh size) performed following the ZooScan methodology. The LOPC counts and sizes particles within 100–2000 μm of spherical equivalent diameter (ESD), whereas the WP2/ZooScan allows for counting, sizing and identification of zooplankton from ~ 400 μm ESD. The difference between the LOPC (all particles) and the WP2/ZooScan (zooplankton only) was assumed to provide the size distribution of non-living particles, whose descriptors were related to a set of explanatory variables (including physical, biological and geographic descriptors). A statistical correction based on these explanatory variables was further applied to the LOPC size distribution in order to remove the non-living particles part, and therefore estimate the size distribution of zooplankton. This extensive data set provides relevant information about the zooplankton size distribution variability, productivity and trophic transfer efficiency in the pelagic ecosystem of the Bay of Biscay at a regional and interannual scale

ONTOLOGY-BASED WEB TOOLS for RETRIEVING PHOTOGRAMMETRIC CULTURAL HERITAGE MODELS

International audienc

Climate Variability and Oceanographic Settings Associated with Interannual Variability in the Initiation of Dinophysis acuminata Blooms

In 2012, there were exceptional blooms of D. acuminata in early spring in what appeared to be a mesoscale event affecting Western Iberia and the Bay of Biscay. The objective of this work was to identify common climatic patterns to explain the observed anomalies in two important aquaculture sites, the Galician Rías Baixas (NW Spain) and Arcachon Bay (SW France). Here, we examine climate variability through physical-biological couplings, Sea Surface Temperature (SST) anomalies and time of initiation of the upwelling season and its intensity over several decades. In 2012, the mesoscale features common to the two sites were positive anomalies in SST and unusual wind patterns. These led to an atypical predominance of upwelling in winter in the Galician Rías, and increased haline stratification associated with a southward advection of the Gironde plume in Arcachon Bay. Both scenarios promoted an early phytoplankton growth season and increased stability that enhanced D. acuminata growth. Therefore, a common climate anomaly caused exceptional blooms of D. acuminata in two distant regions through different triggering mechanisms. These results increase our capability to predict intense diarrhetic shellfish poisoning outbreaks in the early spring from observations in the preceding winter

USING VIRTUAL OR AUGMENTED REALITY for the TIME-BASED STUDY of COMPLEX UNDERWATER ARCHAEOLOGICAL EXCAVATIONS

International audienceCultural Heritage (CH) resources are partial, heterogeneous, discontinuous, and subject to ongoing updates and revisions. The use of semantic web technologies associated with 3D graphical tools is proposed to improve access, exploration, exploitation and enrichment of these CH data in a standardized and more structured form. This article presents the monitoring work developed for more than ten years on the excavation of the Xlendi site. Around an exceptional shipwreck, the oldest from the Archaic period in the Western Mediterranean, we have set up a unique excavation at a depth of 110m assisted by a rigorous and continuous photogrammetry campaign. All the collected results are modelled by an ontology and visualized with virtual and augmented reality tools that allow a bidirectional link between the proposed graphical representations and the non-graphical archaeological data. It is also important to highlight the development of an innovative 3D mobile app that lets users study and understand the site as well as experience sensations close to those of a diver visiting the site

Acremonium strictum Fungaemia in a Paediatric Immunocompromised Patient: Diagnosis and Treatment Difficulties

During the past two decades, an increasing number of unusual moulds has been reported as responsible for septicaemia and systemic or disseminated infections in immunocompromised patients. Investigation of fever in a 10-year-old boy with acute myeloblastic leukaemia, including blood cultures on selective media, allowed the diagnosis of a fungaemia due to the slow-growing fungus Acremonium strictum. The patient recovered with liposomal amphotericin B (AmB) and voriconazole, followed by voriconazole alone due to AmB resistance. Facing a neutropenic patient with fever, clinicians usually suspect bacterial or viral aetiologies. This case, however, illustrates the need for mycological analysis of blood samples in febrile neutropenic patients and for antifungal susceptibility testing

Novel Methodologies for Providing In Situ Data to HAB Early Warning Systems in the European Atlantic Area: The PRIMROSE Experience

Harmful algal blooms (HABs) cause harm to human health or hinder sustainable use of the marine environment in Blue Economy sectors. HABs are temporally and spatially variable and hence their mitigation is closely linked to effective early warning. The European Union (EU) Interreg Atlantic Area project “PRIMROSE”, Predicting Risk and Impact of Harmful Events on the Aquaculture Sector, was focused on the joint development of HAB early warning systems in different regions along the European Atlantic Area. Advancement of the existing HAB forecasting systems requires development of forecasting tools, improvements in data flow and processing, but also additional data inputs to assess the distribution of HAB species, especially in areas away from national monitoring stations, usually located near aquaculture sites. In this contribution, we review different novel technologies for acquiring HAB data and report on the experience gained in several novel local data collection exercises performed during the project. Demonstrations include the deployment of autonomous imaging flow cytometry (IFC) sensors near two aquaculture areas: a mooring in the Daoulas estuary in the Bay of Brest and pumping from a bay in the Shetland Islands to an inland IFC; and several drone deployments, both of Unmanned Aerial Vehicles (UAV) and of Autonomous Surface vehicles (ASVs). Additionally, we have reviewed sampling approaches potentially relevant for HAB early warning including protocols for opportunistic water sampling by coastguard agencies. Experiences in the determination of marine biotoxins in non-traditional vectors and how they could complement standard routine HAB monitoring are also considered.En prens

Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection

BACKGROUND: Chikungunya (CHIK) virus is a mosquito-transmitted alphavirus that causes in humans an acute infection characterised by fever, polyarthralgia, head-ache, and myalgia. Since 2005, the emergence of CHIK virus was associated with an unprecedented magnitude outbreak of CHIK disease in the Indian Ocean. Clinically, this outbreak was characterized by invalidating poly-arthralgia, with myalgia being reported in 97.7% of cases. Since the cellular targets of CHIK virus in humans are unknown, we studied the pathogenic events and targets of CHIK infection in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistology on muscle biopsies from two CHIK virus-infected patients with myositic syndrome showed that viral antigens were found exclusively inside skeletal muscle progenitor cells (designed as satelllite cells), and not in muscle fibers. To evaluate the ability of CHIK virus to replicate in human satellite cells, we assessed virus infection on primary human muscle cells; viral growth was observed in CHIK virus-infected satellite cells with a cytopathic effect, whereas myotubes were essentially refractory to infection. CONCLUSIONS/SIGNIFICANCE: This report provides new insights into CHIK virus pathogenesis, since it is the first to identify a cellular target of CHIK virus in humans and to report a selective infection of muscle satellite cells by a viral agent in humans