Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.

The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population.This work was supported in part by the Spanish AIDS Research Network (RD16/0025/0017, RD16/0025/0018), which is included in the Spanish I+D+I Plan and is co-funded by the ISCIII-Subdirección General de Evaluación and European Funding for Regional Development (FEDER). The sponsors had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the article for publication.S

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Search for magnetic monopoles with ten years of the ANTARES neutrino telescope

This work presents a new search for magnetic monopoles using data taken with the ANTARES neutrino telescope over a period of 10 years (January 2008 to December 2017). Compared to previous ANTARES searches, this analysis uses a run-by-run simulation strategy, with a larger exposure as well as a new simulation of magnetic monopoles taking into account the Kasama, Yang and Goldhaber model for their interaction cross-section with matter. No signal compatible with the passage of relativistic magnetic monopoles is observed, and upper limits on the flux of magnetic monopoles with β=v/c≥0.55, are presented. For ultra-relativistic magnetic monopoles the flux limit is ∼7×10−18 cm−2s−1sr−1

The Power Board of the KM3NeT Digital Optical Module: design, upgrade, and production

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module includes also calibration instruments and electronics for power, readout and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and several prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, 828 until October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. After the validation of a pre-production series, a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure the safe operation at the bottom of the Mediterranean Sea throughout the observatory's lifespa

Probing invisible neutrino decay with KM3NeT-ORCA

In the era of precision measurements of the neutrino oscillation parameters, upcoming neutrino experiments will also be sensitive to physics beyond the Standard Model. KM3NeT/ORCA is a neutrino detector optimised for measuring atmospheric neutrinos from a few GeV to around 100 GeV. In this paper, the sensitivity of the KM3NeT/ORCA detector to neutrino decay has been explored. A three-flavour neutrino oscillation scenario, where the third neutrino mass state $\nu_3$ decays into an invisible state, e.g. a sterile neutrino, is considered. We find that KM3NeT/ORCA would be sensitive to invisible neutrino decays with $1/\alpha_3=\tau_3/m_3 < 180$~$\mathrm{ps/eV}$ at $90\%$ confidence level, assuming true normal ordering. Finally, the impact of neutrino decay on the precision of KM3NeT/ORCA measurements for $\theta_{23}$, $\Delta m^2_{31}$ and mass ordering have been studied. No significant effect of neutrino decay on the sensitivity to these measurements has been found.Comment: 27 pages, 14 figures, bibliography updated, typos correcte

Embedded Software of the KM3NeT Central Logic Board

The KM3NeT Collaboration is building and operating two deep sea neutrino telescopes at the bottom of the Mediterranean Sea. The telescopes consist of latices of photomultiplier tubes housed in pressure-resistant glass spheres, called digital optical modules and arranged in vertical detection units. The two main scientific goals are the determination of the neutrino mass ordering and the discovery and observation of high-energy neutrino sources in the Universe. Neutrinos are detected via the Cherenkov light, which is induced by charged particles originated in neutrino interactions. The photomultiplier tubes convert the Cherenkov light into electrical signals that are acquired and timestamped by the acquisition electronics. Each optical module houses the acquisition electronics for collecting and timestamping the photomultiplier signals with one nanosecond accuracy. Once finished, the two telescopes will have installed more than six thousand optical acquisition nodes, completing one of the more complex networks in the world in terms of operation and synchronization. The embedded software running in the acquisition nodes has been designed to provide a framework that will operate with different hardware versions and functionalities. The hardware will not be accessible once in operation, which complicates the embedded software architecture. The embedded software provides a set of tools to facilitate remote manageability of the deployed hardware, including safe reconfiguration of the firmware. This paper presents the architecture and the techniques, methods and implementation of the embedded software running in the acquisition nodes of the KM3NeT neutrino telescopes