RNAiFold2T: Constraint Programming design of thermo-IRES switches

Motivation: RNA thermometers (RNATs) are cis-regulatory ele- ments that change secondary structure upon temperature shift. Often involved in the regulation of heat shock, cold shock and virulence genes, RNATs constitute an interesting potential resource in synthetic biology, where engineered RNATs could prove to be useful tools in biosensors and conditional gene regulation. Results: Solving the 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, the first Constraint Programming (CP) and Large Neighborhood Search (LNS) algorithms to solve this problem. Benchmarking tests of RNAiFold2T against existent programs (adaptive walk and genetic algorithm) inverse folding show that our software generates two orders of magnitude more solutions, thus allow- ing ample exploration of the space of solutions. Subsequently, solutions can be prioritized by computing various measures, including probability of target structure in the ensemble, melting temperature, etc. Using this strategy, we rationally designed two thermosensor internal ribosome entry site (thermo-IRES) elements, whose normalized cap-independent transla- tion efficiency is approximately 50% greater at 42?C than 30?C, when tested in reticulocyte lysates. Translation efficiency is lower than that of the wild-type IRES element, which on the other hand is fully resistant to temperature shift-up. This appears to be the first purely computational design of functional RNA thermoswitches, and certainly the first purely computational design of functional thermo-IRES elements. Availability: RNAiFold2T is publicly available as as part of the new re- lease RNAiFold3.0 at https://github.com/clotelab/RNAiFold and http: //bioinformatics.bc.edu/clotelab/RNAiFold, which latter has a web server as well. The software is written in C++ and uses OR-Tools CP search engine.Comment: 24 pages, 5 figures, Intelligent Systems for Molecular Biology (ISMB 2016), to appear in journal Bioinformatics 201

Fuzzy logic tuning of a PI controller to improve the performance of a wind turbine on a semi-submersible platform under different wind scenarios

The integration of renewable energy sources in power systems, specially wind energy, is growing as environmental concerns arise in society. Nevertheless, the low amount of viable sites onshore or in shallow waters restricts the use of wind energy. In this sense, offshore semi-submersible platforms appear as an option, which in addition enables the integration of complementary elements, for instance wave energy converters. However, the complexity of the system increases due to the interactions between the platform movements and the wind turbine, and traditional control techniques do not enable to cope with these interactions in an easy way, hence limiting the efficiency of energy harvesting. Intelligent control techniques are an option with a great potential to take full account of the said interactions and to improve energy production efficiency. Still, it is required to have simulation models including those effects beforehand, so that the effects of a designed controller on the system can be evaluated. This paper presents an original fuzzy logic controller that tunes a reference controller, improving its performance according to a developed methodology that allows evaluation of controllers for wind turbines in semi-submersible platforms. The resulting fuzzy logic controller allows higher efficiency concerning mechanical loads in the system, electric energy production and tracking error of the speed reference.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Development and Evaluation of Fuzzy Logic Controllers for Improving Performance of Wind Turbines on Semi-Submersible Platforms under Different Wind Scenarios

Among renewable energy technologies, wind energy features one of the best possibilities for large-scale integration into power systems. However, there are specific restrictions regarding the installation areas for this technology, thus resulting in a growing, yet restricted, rate of penetration of the technology because of the limited viable sites onshore or in shallow waters. In this context, the use of offshore semi-submersible platforms appears as a promising option, which additionally enables the incorporation of other elements, such as wave energy converters or aquaculture. Nevertheless, this kind of offshore facility involves interactions between platform movements and the wind turbine, increasing the complexity of the system, causing traditional control techniques to not be able to fully cope with the dynamics of the system, and thus limiting the efficiency of energy extraction. On the contrary, the use of intelligent control techniques is an interesting option to take full account of the said interactions and to improve energy capture efficiency through the control of the pitch of the blades, especially under turbulent, above-rated wind profiles. This work presents an original fuzzy logic controller that has been validated by comparing it with previously validated controllers, following a developed methodology that allows comparison of controllers for wind turbines in semi-submersible platforms using performance indexes.This work was partially supported by the Ministry of Economy and Competitiveness (Government of Spain) and European Union (RTC-2016-5712-3); by the European Union, CDTI (Spain) and BEISS (UK) through the call H2020 ERA-NET DEMOWIND (WIP10+ project); by the Regional Government of Andalusia and European Union (UMA-CEIATECH-18); and finally, by partial funding for open access charge from the Universidad de Málaga. Partial funding for open access charge: Universidad de Málag

Twelve tips to make successful medical infographics

In the health sciences, professionals must keep up to date to conduct their evidence-based practise. Hence, there is a growing need to share medical knowledge efficiently among healthcare professionals, patients, and undergraduate health science students. Infographics (text and image) are a hybrid element that serves to represent information in an attractive and meaningful visual format. Actually, with the use of the Internet and social networks, infographics have become a popular format for sharing medical information around the world. On the basis of a published literature review, we provide 12 tips in this article to make a successfully health-related infographic with the aim of assisting clinicians, educators, and researchers in their task of communicating and transforming complex information into a visual, attractive, didactic and shareable format. By following these basic recommendations, it is possible to improve the dissemination of scientific and health-related knowledge to different audiences who can benefit from infographics

Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Gener ation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mi tostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nu cleotide change in exon 5 c.1391T>C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insuf ficiency, observed in both brothers, clinically considered as Pearson's syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson's syndrome characteristics and MLASA related phenotypes

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

[EN] Background The microvessels area (MVA), derived from microvascular proliferation, is a biomarker useful for high-grade glioma classification. Nevertheless, its measurement is costly, labor-intense, and invasive. Finding radiologic correlations with MVA could provide a complementary non-invasive approach without an extra cost and labor intensity and from the first stage. This study aims to correlate imaging markers, such as relative cerebral blood volume (rCBV), and local MVA in IDH-wildtype glioblastoma, and to propose this imaging marker as useful for astrocytoma grade 4 classification. Methods Data from 73 tissue blocks belonging to 17 IDH-wildtype glioblastomas and 7 blocks from 2 IDH-mutant astrocytomas were compiled from the Ivy GAP database. MRI processing and rCBV quantification were carried out using ONCOhabitats methodology. Histologic and MRI co-registration was done manually with experts' supervision, achieving an accuracy of 88.8% of overlay. Spearman's correlation was used to analyze the association between rCBV and microvessel area. Mann-Whitney test was used to study differences of rCBV between blocks with presence or absence of microvessels in IDH-wildtype glioblastoma, as well as to find differences with IDH-mutant astrocytoma samples. Results Significant positive correlations were found between rCBV and microvessel area in the IDH-wildtype blocks (p < 0.001), as well as significant differences in rCBV were found between blocks with microvascular proliferation and blocks without it (p < 0.0001). In addition, significant differences in rCBV were found between IDH-wildtype glioblastoma and IDH-mutant astrocytoma samples, being 2-2.5 times higher rCBV values in IDH-wildtype glioblastoma samples. Conclusions The proposed rCBV marker, calculated from diagnostic MRIs, can detect in IDH-wildtype glioblastoma those regions with microvessels from those without it, and it is significantly correlated with local microvessels area. In addition, the proposed rCBV marker can differentiate the IDH mutation status, providing a complementary non-invasive method for high-grade glioma classification.This work was funded by grants from the National Plan for Scientific and Technical Research and Innovation 2017-2020, No. PID2019-104978RB-I00) (JMGG); H2020-SC1-2016-CNECT Project (No. 727560) (JMGG), and H2020SC1-BHC-2018-2020 (No. 825750) (JMGG). M.A.T was supported by DPI201680054-R (Programa Estatal de Promocion del Talento y su Empleabilidad en I + D + i). EFG was supported by the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 844646. The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.Álvarez-Torres, MDM.; Fuster García, E.; Juan-Albarracín, J.; Reynes, G.; Aparici-Robles, F.; Ferrer Lozano, J.; Garcia-Gomez, JM. (2022). Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification. BMC Cancer. 22(1):1-13. https://doi.org/10.1186/s12885-021-09117-411322

Impact of chlorogenic acids from coffee on urine metabolome in healthy human subjects

Several studies suggest that coffee has some benefits for health; however, little is known about the specific role of the main polyphenol compounds of coffee, chlorogenic acids (CGAs), without caffeine interaction. A 1H-Nuclear Magnetic Resonance (1H-NMR)-based metabolomics approach was used to assess the effect of CGAs from coffee on the human urine metabolome. Ten male volunteers participated in a dietary crossover randomized intervention study with a rich CGAs coffee extract beverage (CEB: 223 mg/100 ml of CGAs). The study consisted of a daily intake of CEB or a control beverage with equal caffeine dose during 28 days. Fasting urines collected at the first and last days of each period of the study were analyzed using an CGAs untargeted 1H-NMR approach. Additionally, 4-hour postpandrial urines after the first intake of each beverage were also analyzed. Uni- and multi-variate statistic approaches were used to strengthen the results. Multilevel partial least squares discriminant analysis (ML-PLS-DA) was used to paired comparisons across the crossover design. A further univariate analysis model for crossover studies was performed to assess the significant changes. Acute consumption of CEB resulted in high excretion of 2-furoylglycine, likewise endogenous compounds such as succinic, citric, 3-methyl-2-oxovaleric and isobutyric acids. Sustained consumption of CEB showed an increase of microbiota-derived compounds such as hippuric, 3-(3-Hydroxyphenyl)-3-hydroxypropionic and 3-hydroxyhippuric acids in urine. Moreover, trigonelline was found in urine after both acute and sustained intakes, as well as in the composition of the beverage exhibiting a direct excretion of this biomarker without any biotransformation, suggesting a non-interindividual variation

Elevated Levels of the Complement Activation Product C4d in Bronchial Fluids for the Diagnosis of Lung Cancer

Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95% CI = 0.71-0.94) and 0.67 (95% CI = 0.58-0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95% CI = 0.56-0.83). In conclusion, C4d is consistently elevated in bronchial fluids from lung cancer patients and may be used to improve the diagnosis of the disease

Metabolic signature of a functional high-catechin tea after acute and sustained consumption in healthy volunteers through 1H NMR-based metabolomics analysis of urine.

Functional tea beverages have emerged as a novel approach to achieving health benefits associated with tea. The use of metabolomics may improve the evaluation of their consumption and their effects. The current study aimed to explore the urinary signature of the exposure to a functional high-catechin tea (HCT) using untargeted NMR-based metabolomics. Ten volunteers participated in a crossover intervention study. Individuals consumed an HCT or a control beverage over a period of 28 days. Multilevel partial least squares discriminant analysis (ML-PLS-DA) was used for paired comparisons. A further crossover model was performed to assess the significant changes. The consumption of the HCT resulted in the excretion of theanine, epicatechin, pyrogallol sulfate, higher levels of 3-methyl-2-oxovalerate and succinate, as well as unknown compounds. In conclusion, the present work established novel urinary signatures of a functional drink. Such signatures may be potential biomarkers and/or reflect certain benefits of functional tea beverages