A pilot study identifying a set of microRNAs as precise diagnostic biomarkers of acute kidney injury

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk

EO-Alert: A Satellite Architecture for Detection and Monitoring of Extreme Events in Real Time

This paper presents the architecture and results achieved by the EO-ALERT H2020 project. EO-ALERT proposes the definition and development of the next-generation Earth Observation (EO) data processing chain, based on a novel flight segment architecture that moves optimised key EO data processing elements from the ground segment to onboard the satellite, with the aim of delivering the EO products to the end user with very low latency (in almost real-time). This paper presents the EO-ALERT architecture, its performance and hardware. Performances are presented for two reference user scenarios; ship detection and extreme weather nowcasting/monitoring. The hardware testing results show that, when implemented using Commercial Off-The-Shelf (COTS) components and available communication links, the proposed architecture can deliver EO products and alerts to the end user with a latency lower than one-point-five minutes, for both SAR and Optical Very High Resolution (VHR) missions, demonstrating the viability of the EO-ALERT concept and architecture

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Chiral Symmetry and light resonances in hot and dense matter

We present a study of the $\pi\pi$ scattering amplitude in the $\sigma$ and $\rho$ channels at finite temperature and nuclear density within a chiral unitary framework. Meson resonances are dynamically generated in our approach, which allows us to analyze the behavior of their associated scattering poles when the system is driven towards chiral symmetry restoration. Medium effects are incorporated in three ways: (a) by thermal corrections of the unitarized scattering amplitudes, (b) by finite nuclear density effects associated to a renormalization of the pion decay constant, and complementarily (c) by extending our calculation of the scalar-isoscalar channel to account for finite nuclear density and temperature effects in a microscopic many-body implementation of pion dynamics. Our results are discussed in connection with several phenomenological aspects relevant for nuclear matter and Heavy-Ion Collision experiments, such as $\rho$ mass scaling vs broadening from dilepton spectra and chiral restoration signals in the $\sigma$ channel. We also elaborate on the molecular nature of $\pi\pi$ resonances.Comment: 14 pages, 14 figures. Contribution to Hard Probes 2008, Illa de A Toxa, Spain, June 8th-14th 200

EO-ALERT: A Novel Architecture for the Next Generation of Earth Observation Satellites Supporting Rapid Civil Alerts

The EO-ALERT project proposes the definition and development of the next-generation Earth Observation (EO) data processing chain, based on a novel flight segment architecture that moves opti-mised key EO data processing elements from the ground segment to on-board the satellite, with the aim of delivering EO products to the end user with very low latency. EO-ALERT achieves, globally, latencies below five minutes for EO products delivery, and below 1 minute in some scenarios. The proposed archi-tecture combines innovations in the on-board elements of the data chain and the communications, namely: on-board reconfigurable data handling, on-board image generation and processing for the generation of alerts (EO products) using Artificial Intelligence (AI), on-board AI-based data compression and encryption, high-speed on-board avionics, and reconfigurable high data rate communication links to ground, including a separate chain for alerts with minimum latency and global coverage. This paper pre-sents the proposed architecture, its performance and hardware, considering two different user scenarios: ship detection and extreme weather nowcasting. The results show that, when implemented using COTS components and available communication links, the proposed architecture can deliver alerts to ground with latency below five minutes, for both SAR and Optical missions, demonstrating the viability of the EO-ALERT concept

A Novel Satellite Architecture for the Next Generation of Earth Observation Satellites Supporting Rapid Alerts

The EO-ALERT European Commission H2020 project proposes the definition, development, and verification and validation through ground hardware testing, of a next-generation Earth Observation (EO) data processing chain. The proposed data processing chain is based on a novel flight segment architecture that moves EO data processing elements traditionally executed in the ground segment to on-board the satellite, with the aim of delivering EO products to the end user with very low latency. EO-ALERT achieves, globally, latencies below five minutes for EO products delivery, and below one minute in realistic scenarios. The proposed EO-ALERT architecture is enabled by on-board processing, recent improvements in processing hardware using Commercial Off-The-Shelf (COTS) components, and persistent space-to-ground communications links. EO-ALERT combines innovations in the on-board elements of the data chain and the communications, namely: on-board reconfigurable data handling, on-board image generation and processing for the generation of alerts (EO products) using Machine Learning (ML) and Artificial Intelligence (AI), on-board AI-based data compression and encryption, high-speed on-board avionics, and reconfigurable high data rate communication links to ground, including a separate chain for alerts with minimum latency and global coverage. This paper presents the proposed architecture, its hardware realization for the ground testing in a representative environment and its performance. The architecture’s performance is evaluated considering two different user scenarios where very low latency (almost-real-time) EO product delivery is required: ship detection and extreme weather monitoring/nowcasting. The hardware testing results show that, when implemented using COTS components and available communication links, the proposed architecture can deliver alerts to the end user with a latency below five minutes, for both SAR and Optical missions, demonstrating the viability of the EO-ALERT architecture. In particular, in several test scenarios, for both the TerraSAR-X SAR and DEIMOS-2 Optical Very High Resolution (VHR) missions, hardware testing of the proposed architecture has shown it can deliver EO products and alerts to the end user globally, with latency lower than one-point-five minutes

Characterisation of the Putative Effector Interaction Site of the Regulatory HbpR Protein from Pseudomonas azelaica by Site-Directed Mutagenesis

Bacterial transcription activators of the XylR/DmpR subfamily exert their expression control via σ54-dependent RNA polymerase upon stimulation by a chemical effector, typically an aromatic compound. Where the chemical effector interacts with the transcription regulator protein to achieve activation is still largely unknown. Here we focus on the HbpR protein from Pseudomonas azelaica, which is a member of the XylR/DmpR subfamily and responds to biaromatic effectors such as 2-hydroxybiphenyl. We use protein structure modeling to predict folding of the effector recognition domain of HbpR and molecular docking to identify the region where 2-hydroxybiphenyl may interact with HbpR. A large number of site-directed HbpR mutants of residues in- and outside the predicted interaction area was created and their potential to induce reporter gene expression in Escherichia coli from the cognate PC promoter upon activation with 2-hydroxybiphenyl was studied. Mutant proteins were purified to study their conformation. Critical residues for effector stimulation indeed grouped near the predicted area, some of which are conserved among XylR/DmpR subfamily members in spite of displaying different effector specificities. This suggests that they are important for the process of effector activation, but not necessarily for effector specificity recognition

Role of small-sized phytoplankton in triggering an ecosystem disruptive algal bloom in a Mediterranean hypersaline coastal lagoon

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<i>Gaia</i> Data Release 1. Summary of the astrometric, photometric, and survey properties

Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues – a realisation of the Tycho-Gaia Astrometric Solution (TGAS) – and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of ∼3000 Cepheid and RR-Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr−1 for the proper motions. A systematic component of ∼0.3 mas should be added to the parallax uncertainties. For the subset of ∼94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr−1. For the secondary astrometric data set, the typical uncertainty of the positions is ∼10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to ∼0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data