Circular RNA-centered regulatory networks in the physiopathology of cardiovascular diseases

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Non-coding regulatory RNAs are generated as a core output of the eukaryotic genomes, being essential players in cell biology. At the organism level, they are key functional actors in those tissues and organs with limited proliferation capabilities such as the heart. The role of regulatory networks mediated by non-coding RNAs in the pathophysiology of cardiovascular conditions is starting to be unveiled. However, a deeper knowledge of the functional interactions among the diverse non-coding RNA families and their phenotypic consequences is required. This review presents the current knowledge about the functional crosstalk between circRNAs and other biomolecules in the framework of the cardiovascular diseases.This work is supported by COST (European Cooperation in Science and Technology) Action EU-CardioRNA CA17129 and Portuguese Foundation for Science and Technology (FCT) under the framework of the research grant PTDC-MED-GEN-29389-2017.info:eu-repo/semantics/publishedVersio

Interspecies communication in holobionts by non-coding RNA exchange

PTDC-MED-GEN-29389-2017Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.publishersversionpublishe

Impact of SM parameters and of the vacua of the Higgs potential in gravitational waves detection

In this work we discuss two different phases of a complex singlet extension of the Standard Model (SM) together with an extension that also includes new fermion fields, in particular, a Majoron model equipped with an inverse seesaw mechanism. All considered scenarios contain a global $\mathrm{U}(1)$ symmetry and allow for first-order phase transitions while only two of them are strong enough to favour the detection of primordial gravitational waves (GWs) in planned experiments such as LISA. In particular, this is shown to be possible in the singlet extension with a non vanishing real VEV at zero temperature and also in the model with extra fermions. In the singlet extension with no additional fermions, the detection of GWs strongly depends on the $\mathrm{U}(1)$ symmetry breaking pattern of the scalar potential at zero temperature. We study for the first time the impact of the precision in the determination of the SM parameters on the strength of the GWs spectrum. It turns out that the variation of the SM parameters such as the Higgs boson mass and top quark Yukawa coupling in their allowed experimental ranges has a notable impact on GWs detectability prospects.Comment: 28 pages, 13 figure

Helping WWTP managers to address the volatile methylsiloxanes issue-Behaviour and complete mass balance in a conventional plant

Volatile methylsiloxanes (VMSs) are a group of additives employed in different consumer products that can affect the quality of the biogas produced in wastewater treatment plants (WWTPs). The main objective of this study is to understand the fate of different VMSs along the treatment process of a WWTP located in Aveiro (Portugal). Thus, wastewater, sludge, biogas, and air were sampled in different units for two weeks. Subsequently, these samples were extracted and analyzed by different environment-friendly protocols to obtain their VMS (L3-L5, D3-D6) concentrations and profiles. Finally, considering the different matrix flows at every sampling moment, the mass distribution of VMSs within the plant was estimated. The levels of ∑VMSs were similar to those showed in the literature (0.1-50 μg/L in entry wastewater and 1-100 μg/g dw in primary sludge). However, the entry wastewater profile showed higher variability in D3 concentrations (from non detected to 49 μg/L) than found in previous studies (0.10-1.00 μg/L), likely caused by isolated releases of this compound that could be related to industrial sources. Outdoor air samples showed a prevalence of D5, while indoor air locations were characterized by a predominance of D3 and D4. Differences in sources and the presence of an indoor air filtration system may explain this divergence. Biogas was characterized by ∑VMSs concentrations (8.00 ± 0.22 mg/m3) above the limits recommended by some engine manufacturers and mainly composed of D5 (89%). Overall, 81% of the total incoming mass of VMSs is reduced along the WWTP, being the primary decanter and the secondary treatment responsible for the highest decrease (30.6% and 29.4% of the initial mass, respectively). This reduction, however, is congener dependant. The present study demonstrates the importance of extending sampling periods and matrices (i.e., sludge and air) to improve sample representativity, time-sensitivity, and the accuracy of mass balance exercises.This work was financially supported by: (i) Projects LA/P/0045/2020 (ALiCE – Associated Laboratory in Chemical Engineering) and UIDB/00511/2020 and UIDP/00511/2020 (LEPABE – Laboratory for Process Engineering, Environment, Biotechnology and Energy), funded by national funds through FCT/MCTES (PIDDAC); (ii) Project LANSILOT (PTDC/CTA-AMB/32084/2017; POCI-01–0145-FEDER-032084), funded by FEDER through COMPETE2020—Programa Operacional Competitividade e Internacionalizaçao(POCI) and by national funds (PIDDAC) through FCT/MCTES; (iii) Project “HealthyWaters – Identification, Elimination, Social Awareness and Education of Water Chemical and Biological Micropollutants with Health and Environmental Implications” (NORTE-01-0145-FEDER-000069), co-financed by Programa Operacional Regional do Norte (NORTE 2020), through Portugal 2020 and FEDER; (iv) N. Ratola thanks FCT for the financial support of his work contract through the Scientific Employment Stimulus -Institutional Call - [CEECINST/00049/2018]; (v) G. Pantuzza thanks FCT PhD programme for Grant 2020.07815.BD, supported under the Portugal 2020 Partnership Agreement and European Social Fund (ESF); (vi) V. Homem thanks national funds through FCT, under the Scientific Employment Stimulus—Individual Call - CEECIND/00676/2017. The authors wish to thank the help of the staff at the WWTP in the design of the sampling strategy and the collection of the samples.S

Circulating miRNAs are associated with the systemic extent of atherosclerosis : novel observations for miR-27b and miR-146

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four participants were prospectively recruited and divided into five age- and sex-matched groups: presenting no atherosclerosis, isolated coronary atherosclerosis, coronary and lower extremity atherosclerosis, coronary and carotid atherosclerosis, and atherosclerosis of the coronary, lower extremity, and carotid territories. The expression of six circulating miRNAs with distinct biological roles was assessed. The expression of miR-27b and miR-146 differed across groups (p < 0.05), showing a decrease in the presence of atherosclerosis, particularly in the three territories. miR-27b and miR-146 expression decreased in association with a higher severity of coronary, lower extremity, and carotid atherosclerosis. Polyvascular atherosclerosis involving the three territories was independently associated with a decreased miR-27b and miR-146 expression. Both miRNAs presented an area under the curve of ≥0.75 for predicting polyvascular atherosclerosis involving the three territories. To conclude, miR-27b and miR-146 were associated with the presence of severe polyvascular atherosclerosis and with the atherosclerosis severity in each territory. Both are potential biomarkers of severe systemic atherosclerosis.info:eu-repo/semantics/publishedVersio

Association between mir-146a and tumor necrosis factor alpha (Tnf-α) in stable coronary artery disease

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7–1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (∆Ct) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ∆Ct miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.publishersversionpublishe

Cigarette smoking, miR-27b downregulation, and peripheral artery disease : insights into the mechanisms of smoking toxicity

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation.info:eu-repo/semantics/publishedVersio

Impact of cardiology referral: clinical outcomes and factors associated with physicians' adherence to recommendations

OBJECTIVES: Cardiology referral is common for patients admitted for non-cardiac diseases. Recommendations from cardiologists may involve complex and aggressive treatments that could be ignored or denied by other physicians. The purpose of this study was to compare the outcomes of patients who were given recommendations during cardiology referrals and to examine the clinical outcomes of patients who did not follow the recommendations. METHODS: We enrolled 589 consecutive patients who received in-hospital cardiology consultations. Data on recommendations, implementation of suggestions and outcomes were collected. RESULTS: Regarding adherence of the referring service to the recommendations, 77% of patients were classified in the adherence group and 23% were classified in the non-adherence group. Membership in the non-adherence group (

Hybrid cascade heat pump and thermal-electric energy storage system for residential buildings: experimental testing and performance analysis

The need for innovative heating and cooling systems to decarbonize the building sector is widely recognized. It is especially important to increase the share of renewables at building level by maximizing self-consumption and reducing the primary energy demand. Accordingly, in the present paper, the results on a wide experimental campaign on a hybrid system are discussed. The system included a sorption module working as the topping cycle in a cascade configuration with a DC-driven vapor compression heat pump. A three-fluids heat exchanger with a phase change material (PCM), i.e., RT4 with nominal melting temperature of 4 °C, was installed on the evaporator side of the heat pump, for simultaneous operation as thermal storage and heat pumping purposes. The heat pump was connected to a DC-bus that included PV connection and electricity storage (batteries). Results showed that the energy efficiency of the heat pump in cascade operation was double compared to compression-only configuration and that, when simultaneously charging and discharging the latent storage in cascade configuration, no penalization in terms of efficiency compared to the compression-only configuration was measured. The self-sufficiency of the system was evaluated for three reference weeks in summer conditions of Athens climate and it was found that up to 100% of the electricity needed to drive the system could be self-produced for a modest cooling demand and up to 67% for the warmer conditions with high cooling demand.This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 768824 (HYBUILD). This work was partially funded by the Ministerio de Ciencia, Innovación y Universidades de España (RTI2018-093849-B-C31) and by the Ministerio de Ciencia, Innovación y Universidades—Agencia Estatal de Investi-gación (AEI) (RED2018-102431-T). GREiA is certified agent TECNIO in the category of technology developers from the Government of Catalonia. This work is partially supported by ICREA under the ICREA Academia program

Linkage disequilibrium and population structure in wild and cultivated populations of rubber tree (Hevea brasiliensis).

Abstract: Among rubber tree species, which belong to the Hevea genus of the Euphorbiaceae family, Hevea brasiliensis (Willd. ex Adr.de Juss.) Muell. Arg. is the main commercial source of natural rubber production worldwide. Knowledge of the population structure and linkage disequilibrium (LD) of this species is essential for the efficient organization and exploitation of genetic resources. Here, we obtained single-nucleotide polymorphisms (SNPs) using a genotyping-by-sequencing (GBS) approach and then employed the SNPs for the following objectives: (i) to identify the positions of SNPs on a genetic map of a segregating mapping population, (ii) to evaluate the population structure of a germplasm collection, and (iii) to detect patterns of LD decay among chromosomes for future genetic association studies in rubber tree. A total of 626 genotypes, including both germplasm accessions (368) and individuals from a genetic mapping population (254), were genotyped. A total of 77,660 and 21,283 SNPs were detected by GBS in the germplasm and mapping populations, respectively. The mapping population, which was previously mapped, was constructed with 1,062 markers, among which only 576 SNPs came from GBS, reducing the average interval between two adjacent markers to 4.4 cM. SNPs from GBS genotyping were used for the analysis of genetic structure and LD estimation in the germplasm accessions. Two groups, which largely corresponded to the cultivated and wild populations, were detected using STRUCTURE and via principal coordinate analysis. LD analysis, also using the mapped SNPs, revealed that non-random associations varied along chromosomes, with regions of high LD interspersed with regions of low LD. Considering the length of the genetic map (4,693 cM) and the mean LD (0.49 for cultivated and 0.02 for wild populations), a large number of evenly spaced SNPs would be needed to perform genome-wide association studies in rubber tree, and the wilder the genotypes used, the more difficult the mapping saturation