EZH2 and BMI1 inversely correlate with prognosis and TP53 mutation in breast cancer

Introduction PolycombGroup (PcG) proteins maintain gene repression through histone modifications and have been implicated in stem cell regulation and cancer. EZH2 is part of Polycomb Repressive Complex 2 (PRC2) and trimethylates H3K27. This histone mark recruits the BMI1-containing PRC1 that silences the genes marked by PRC2. Based on their role in stem cells, EZH2 and BMI1 have been predicted to contribute to a poor outcome for cancer patients. Methods We have analysed the expression of EZH2 and BMI1 in a well-characterised dataset of 295 human breast cancer samples. Results Interestingly, although EZH2 overexpression correlates with a poor prognosis in breast cancer, BMI1 overexpression correlates with a good outcome. Although this may reflect transformation of different cell types, we also observed a functional difference. The PcG-target genes INK4A and ARF are not expressed in tumours with high BMI1, but they are expressed in tumours with EZH2 overexpression. ARF expression results in tumour protein P53 (TP53) activation, and we found a significantly higher proportion of TP53 mutations in tumours with high EZH2. This may explain why tumours with high EZH2 respond poorly to therapy, in contrast to tumours with high BMI1. Conclusions Overall, our data highlight that whereas EZH2 and BMI1 may function in a 'linear' pathway in normal development, their overexpression has different functional consequences for breast tumourigenesi

BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A

10.1186/bcr2354Breast Cancer Research114R6

Deep-Sea Bioluminescence Blooms after Dense Water Formation at the Ocean Surface

<p>The deep ocean is the largest and least known ecosystem on Earth. It hosts numerous pelagic organisms, most of which are able to emit light. Here we present a unique data set consisting of a 2.5-year long record of light emission by deep-sea pelagic organisms, measured from December 2007 to June 2010 at the ANTARES underwater neutrino telescope in the deep NW Mediterranean Sea, jointly with synchronous hydrological records. This is the longest continuous time-series of deep-sea bioluminescence ever recorded. Our record reveals several weeks long, seasonal bioluminescence blooms with light intensity up to two orders of magnitude higher than background values, which correlate to changes in the properties of deep waters. Such changes are triggered by the winter cooling and evaporation experienced by the upper ocean layer in the Gulf of Lion that leads to the formation and subsequent sinking of dense water through a process known as "open-sea convection". It episodically renews the deep water of the study area and conveys fresh organic matter that fuels the deep ecosystems. Luminous bacteria most likely are the main contributors to the observed deep-sea bioluminescence blooms. Our observations demonstrate a consistent and rapid connection between deep open-sea convection and bathypelagic biological activity, as expressed by bioluminescence. In a setting where dense water formation events are likely to decline under global warming scenarios enhancing ocean stratification, in situ observatories become essential as environmental sentinels for the monitoring and understanding of deep-sea ecosystem shifts.</p>

Deep-Sea Bioluminescence Blooms after Dense Water Formation at the Ocean Surface

The deep ocean is the largest and least known ecosystem on Earth. It hosts numerous pelagic organisms, most of which are able to emit light. Here we present a unique data set consisting of a 2.5-year long record of light emission by deep-sea pelagic organisms, measured from December 2007 to June 2010 at the ANTARES underwater neutrino telescope in the deep NW Mediterranean Sea, jointly with synchronous hydrological records. This is the longest continuous time-series of deep-sea bioluminescence ever recorded. Our record reveals several weeks long, seasonal bioluminescence blooms with light intensity up to two orders of magnitude higher than background values, which correlate to changes in the properties of deep waters. Such changes are triggered by the winter cooling and evaporation experienced by the upper ocean layer in the Gulf of Lion that leads to the formation and subsequent sinking of dense water through a process known as “open-sea convection”. It episodically renews the deep water of the study area and conveys fresh organic matter that fuels the deep ecosystems. Luminous bacteria most likely are the main contributors to the observed deep-sea bioluminescence blooms. Our observations demonstrate a consistent and rapid connection between deep open-sea convection and bathypelagic biological activity, as expressed by bioluminescence. In a setting where dense water formation events are likely to decline under global warming scenarios enhancing ocean stratification, in situ observatories become essential as environmental sentinels for the monitoring and understanding of deep-sea ecosystem shifts

KM3NeT front-end and readout electronics system: hardware, firmware, and software

he KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host water-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large volume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced by neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for calibration of the photomultiplier signal and positioning of the optical module, and all associated electronics boards. By design, the total electrical power consumption of an optical module has been capped at seven Watts. We present an overview of the front-end and readout electronics system inside the optical module, which has been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life time of at least 20 years

Architecture and performance of the KM3NeT front-end firmware

The KM3NeT infrastructure consists of two deep-sea neutrino telescopes being deployed in the Mediterranean Sea. The telescopes will detect extraterrestrial and atmospheric neutrinos by means of the incident photons induced by the passage of relativistic charged particles through the seawater as a consequence of a neutrino interaction. The telescopes are configured in a three-dimensional grid of digital optical modules, each hosting 31 photomultipliers. The photomultiplier signals produced by the incident Cherenkov photons are converted into digital information consisting of the integrated pulse duration and the time at which it surpasses a chosen threshold. The digitization is done by means of time to digital converters (TDCs) embedded in the field programmable gate array of the central logic board. Subsequently, a state machine formats the acquired data for its transmission to shore. We present the architecture and performance of the front-end firmware consisting of the TDCs and the state machine

KM3NeT front-end and readout electronics system: hardware, firmware, and software

The KM3NeT research infrastructure being built at the bottom of the Mediterranean Sea will host water-Cherenkov telescopes for the detection of cosmic neutrinos. The neutrino telescopes will consist of large volume three-dimensional grids of optical modules to detect the Cherenkov light from charged particles produced by neutrino-induced interactions. Each optical module houses 31 3-in. photomultiplier tubes, instrumentation for calibration of the photomultiplier signal and positioning of the optical module, and all associated electronics boards. By design, the total electrical power consumption of an optical module has been capped at seven Watts. We present an overview of the front-end and readout electronics system inside the optical module, which has been designed for a 1-ns synchronization between the clocks of all optical modules in the grid during a life time of at least 20 year

Time series of oceanographic parameters measured at the Lacaze-Duthiers Canyon (LDC) and the open-sea convection region in the Gulf of Lion (LION) from January 2008 to June 2010.

<p>(<b>a</b>) Potential temperature at 500 and 1,000 m depth at the LDC mooring site and (<b>b</b>) from various water depths at the LION site, jointly with (<b>c</b>) salinity at 2,300 m depth, (<b>d</b>) horizontal current speed and (<b>e</b>) vertical current speed from various water depths at the LION site. The four levels of temperature measurements at LION presented here are a sub-set of measurement depths (see Fig. S1). Essentially stable temperatures in the deepest layers in 2008 show that open-sea convection reached only 700 m and did not modify the deep water in the study area. In contrast, strong convection events, reaching 2,300 m depth, occurred during February-March 2009 and 2010 with an abrupt cooling of the upper water column and an increase in temperature and salinity in the deep layers. A concurrent increase in current speed was also noticed in winter 2009 and 2010. The 5-month long data gap in 2009 is due to a damaging of the mooring line during the April 2009 recovery, which induced a postponement of its redeployment to September 2009.</p