Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells

This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.Due to its ability to regulate the growth, differentiation and apoptosis of cancer cells, retinoic acid (RA) is considered a signaling molecule with promising therapeutic potential in oncology. In this study, we show that RA is able to induce the intrinsic ability of breast cancer cells to recognize double-stranded RNA (dsRNA) through the upregulation of Toll-like receptor 3 (TLR3) expression. RA, co-administered with the dsRNA mimicker polyinosinic–polycytidylic acid (poly(I:C)), synergizes to mount a specific response program able to sense dsRNA through the concurrent upregulation of TLR3, the dsRNA helicases melanoma differentiation-associated antigen-5 (MDA-5) and RA-inducible gene-1 (RIG-1), and the dsRNA-activated protein kinase (PKR) expression, leading breast cancer cells to specifically express downstream transcriptional targets of dsRNA sensors, such as interferon-β (IFNβ), interleukin-8 (IL-8), chemokine (C-C motif) ligand 5 (CCL5), and C-X-C motif Chemokine 10 (CXCL10). A TLR3-dependent apoptotic program is also induced by RA and poly(I:C) co-treatment that correlates with the induction of the tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and contributes to block breast cancer cell proliferation. The mechanisms of apoptosis induced by RA/poly(I:C) in breast cancer cells involve type I IFN autocrine signaling, caspase-8 and caspase-3 activation, as well as TRAIL signaling. Our results reveal important links among RA, TLR3 and TRAIL and highlight the combined use of RA and poly(I:C) as a potential effective tumor therapy by improving the apoptotic response of cancer cells with low sensitivity to the action of synthetic dsRNA.This work was supported by funds from the MICINN (SAF2007-63634 and SAF2010-21195), CSIC (201120E105), and Fundación Médica Mutua Madrileña (2005 0584). ARBV was supported by funds from the MICINN. AMJ-L is a recipient of a grant from the Spanish MICINN (Ramón y Cajal Program).Peer reviewe

Revisiting compact RDF stores based on k2-trees

We present a new compact representation to efficiently store and query large RDF datasets in main memory. Our proposal, called BMatrix, is based on the k2-tree, a data structure devised to represent binary matrices in a compressed way, and aims at improving the results of previous state-of-the-art alternatives, especially in datasets with a relatively large number of predicates. We introduce our technique, together with some improvements on the basic k2-tree that can be applied to our solution in order to boost compression. Experimental results in the flagship RDF dataset DBPedia show that our proposal achieves better compression than existing alternatives, while yielding competitive query times, particularly in the most frequent triple patterns and in queries with unbound predicate, in which we outperform existing solutions.Comment: This research has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Actions H2020-MSCA-RISE-2015 BIRDS GA No. 69094

Space/time-efficient RDF stores based on circular suffix sorting

In recent years, RDF has gained popularity as a format for the standardized publication and exchange of information in the Web of Data. In this paper we introduce RDFCSA, a data structure that is able to self-index an RDF dataset in small space and supports efficient querying. RDFCSA regards the triples of the RDF store as short circular strings and applies suffix sorting on those strings, so that triple-pattern queries reduce to prefix searching on the string set. The RDF store is then represented compactly using a Compressed Suffix Array (CSA), a proved technology in text indexing that efficiently supports prefix searches. Our experimental evaluation shows that RDFCSA is able to answer triple-pattern queries in a few microseconds per result while using less than 60% of the space required by the raw original data. We also support join queries, which provide the basis for full SPARQL query support. Even though smaller-space solutions exist, as well as faster ones, RDFCSA is shown to provide an excellent space/time tradeoff, with fast and consistent query times within much less space than alternatives that compete in time.Comment: This work has been submitted to the IEEE TKDE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Extending General Compact Querieable Representations to GIS Applications

The raster model is commonly used for the representation of images in many domains, and is especially useful in Geographic Information Systems (GIS) to store information about continuous variables of the space (elevation, temperature, etc.). Current representations of raster data are usually designed for external memory or, when stored in main memory, lack efficient query capabilities. In this paper we propose compact representations to efficiently store and query raster datasets in main memory. We present different representations for binary raster data, general raster data and time-evolving raster data. We experimentally compare our proposals with traditional storage mechanisms such as linear quadtrees or compressed GeoTIFF files. Results show that our structures are up to 10 times smaller than classical linear quadtrees, and even comparable in space to non-querieable representations of raster data, while efficiently answering a number of typical queries.Comment: This research has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Actions H2020-MSCA-RISE-2015 BIRDS GA No. 690941

Serum amyloid P component promotes formation of distinct aggregated lysozyme morphologies and reduces toxicity in Drosophila flies expressing F57I lysozyme.

Many conflicting reports about the involvement of serum amyloid P component (SAP) in amyloid diseases have been presented over the years; SAP is known to be a universal component of amyloid aggregates but it has been suggested that it can both induce and suppress amyloid formation. By using our Drosophila model of systemic lysozyme amyloidosis, SAP has previously been shown to reduce the toxicity induced by the expression of the disease-associated lysozyme variant, F57I, in the Drosophila central nervous system. This study further investigates the involvement of SAP in modulating lysozyme toxicity using histochemistry and spectral analyses on the double transgenic WT and F57I lysozyme flies to probe; i) formation of aggregates, ii) morphological differences of the aggregated lysozyme species formed in the presence or absence of SAP, iii) location of lysozyme and iv) co-localisation of lysozyme and SAP in the fly brain. We found that SAP can counteract the toxicity (measured by the reduction in the median survival time) induced by F57I lysozyme by converting toxic F57I species into less toxic amyloid-like structures, as reflected by the spectral changes that p-FTAA undergoes when bound to lysozyme deposits in F57I-F57I-SAP flies as compared to F57I-F57I flies. Indeed, when SAP was introduced to in vitro lysozyme fibril formation, the endpoint fibrils had enhanced ThT fluorescence intensity as compared to lysozyme fibrils alone. This suggests that a general mechanism for SAP's role in amyloid diseases may be to promote the formation of stable, amyloid-like fibrils, thus decreasing the impact of toxic species formed along the aggregation pathway

Session D2: Coimbra Fishway: Restoring Connectivity in River Mondego

Abstract: River Mondego is the largest Portuguese river with its basin entirely within national territory. The Açude-Ponte dam was built in Mondego in the 80’s, along with three other large dams to mitigate floods and to allow the integrated use of river basin water resources for hydroelectric power generation, public supply, industry and irrigation. Considering the river importance for several fish species, namely sea-lamprey and shad, a fishway was constructed. Several structural and hydraulic problems soon revealed that this fishway was inefficient therefore this dam became the first impassable obstacle in the River Mondego. In 2011, after several years of biological and hydraulic monitoring, and once the reasons for the fishway inefficiency were perfectly identified, a vertical-slot fishway was built to restore river connectivity. The efficiency and effectiveness of the Coimbra Fishway has been studied since 2012 using several monitoring techniques (visual counts, biotelemetry techniques and CPUE abundance with electrofishing). Monitoring results show that several autochthonous species use the fishway, including the diadromous sea-lamprey, allis and twaite shad and European-eel. More than 1,500.000 fish have used the fishway during the upstream or downstream migration. PIT telemetry has shown an efficiency of 30% for Petromyzon marinus and 14% for Luciobarbus bocagei. Pre and post fishway construction electrofishing monitoring shows improvements in sealamprey larvae abundance both upstream and downstream from the Açude-Ponte dam. Coimbra Fishway project is improving fish migration in River Mondego, but it’s also an integrated project involving other important aspects such as fisheries and river basin management and environmental education. Changes in exploitation regimes of upstream hydropower dams and in the Açude-Ponte are also planned to increase the fishway efficiency. Finally, several activities have been carried out in association with this project to raise public awareness regarding environmental issues, particularly those related with river longitudinal continuity

Development and Optimization of an Online SPE-HPLC-FD Method for Quantification of Fluoroquinolones in Wastewater Effluents

Fluoroquinolones are antimicrobial agents widely found in environmental matrices and extensively studied due to their persistence and implications for multiresistant bacteria. The presence of fluoroquinolones in the environment is mainly due to the incapability of wastewater treatment plants (WWTPs) to completely remove those compounds. The amount of fluoroquinolones released through effluents depends on the type of treatment used by the WWTPs. So, accurate analytical methods to quantify those compounds on WWTPs process and in effluents are crucial. Solid phase extraction (SPE) coupled to liquid chromatography is a straightforward technique that provides analyte extraction, cleanup, separation and detection while providing a good reproducibility and efficiency. The purpose of this work was the establishment of a novel method for quantification of Ofloxacin, Norfloxacin, Ciprofloxacin and Moxifloxacin on WWTPs effluents using on-line SPE. Samples were injected directly on a restricted access material column LichroCart 25-4 Lichrospher® RP-18 ADS (25 μm) and then transferred to an analytical column Luna PFP (2) (150 x 4.6 mm ID, 100 Å, 3 μm) for separation in isocratic mode with a mixture of 0.1% triethylamine in water (acidified to pH = 2.2 with trifluoroacetic acid) and ethanol as mobile phase; column oven was set at 45ºC. The detection was performed by fluorescence with an excitation wavelength of 290 nm and an emission wavelength of 460 nm. The injection volume of 100 μL of previous preconcentrated sample was compared with larger volume injection of only filtered effluent samples. The study was conducted with effluent samples collected from a municipal WWTP in the north of Portugal

Session D1: Modelling the Efficiency of a Vertical Slot Fishway for Anadromous Fishes

Abstract: Several types of fish passage are increasingly being installed in river barriers to restore the longitudinal connectivity of fragmented riverine habitats. A vertical slot fishway installed in the Açude-Ponte weir at Coimbra (River Mondego, Portugal) was monitored to model the efficiency of this infrastructure for anadromous fishes (i.e., sea lamprey Petromyzon marinus L.; allis shad Alosa alosa L. and twaite shad Alosa fallax Lacépède, 1800) throughout 2013 and 2014 spawning seasons. Fish passage was assessed using a video recording system. Simultaneously, eight abiotic parameters, considered as potential predictors of fishway’s use by anadromous fishes, were continuously recorded during the entire study period. Boosted Regression Trees (BRTs) analysis was applied to relate the use of the fishway by sea lamprey and Alosa spp. with the abiotic predictors. To complement this data, a passive integrated transponder (PIT) antenna system was used to quantify passage efficiency for sea lampreys. Size frequency distribution and total biomass of fishes that successfully transposed the fishway was also estimated. Video data show that in the migratory seasons of 2013 and 2014, 8333 and 21979 sea lampreys passed through fishway, respectively, and a total of 7503 and 3404 Alosa spp. individuals transposed this infrastructure during the same period. About 30% of PIT tagged lampreys transposed the fishway. BRT models identified the river flow as the most important variable to explain use of the fishway by anadromous fishes. The relationships of this variable with the fish passages suggest that sea lampreys and Alosa spp. use the fishway preferentially at relatively low flow conditions that maximize the attraction efficiency of the fishway entrance. Finally, results obtained with this study were used to implement a sub-sampling methodology (video processing) to estimate the total amount of fish (lamprey and shads) that annually use the fishway during their spawning migrations

Temporal patterns of the catadromous thinlip grey mullet migration in freshwater

The thinlip grey mullet (Chelon ramada Risso, 1827) is a catadromous fish that performs massive migrations to freshwater habitats for feeding purposes that can assume a structuring role on riverine ecology due to the biomass involved in these movements. Seasonal movements of thinlip grey mullet through a vertical slot fish pass located in River Mondego (Portugal) were continuously monitored between 2013 and 2017. The extent of trophic migration, population size structure, biomass and the environmental triggers of bi-directional species' migratory activity were analysed. Between March and November of 2013/2014, ~2 million and 1 million movements were respectively recorded. From a subsampling approach, the upstream movements between 2015 and 2017 were estimated. Annually, around five hundred thousand upstream movements can occur to provide species access to the upstream freshwater reaches. Movements are exclusively diurnal, and the population composed by young adults in their first year of maturity, yet juveniles and larger fish were present (TL range: 90–540 mm). Upstream movements increased with temperatures above 15°C, reaching a peak at around 20°C coupled with a photoperiod of 15 h. Downstream movements attained the higher rates when temperature dropped from 22°C to 20°C and photoperiod to 13 h. However, under wetter hydrological conditions (as in 2014), discharge flows have a higher influence. These finding provide unique information regarding species migration to freshwater habitats in the Atlantic coast, namely the extended periods spent in such environments, overlapping with the spawning migration period. Additionally, highlights the importance of species' trophic migration both for its life cycle and riverine food-web