Evaluation of two MM5-PBL parameterizations for solar radiation and temperature estimation in the South-Eastern area of the Iberian Peninsula

We study the relative performance of two different MM5-PBL parameterizations (Blackadar and MRF) simulating hourly values of solar irradiance and temperature in the south-eastern part of the Iberian Peninsula. The evaluation was carried out throughout the different seasons of the year 2005 and for three different sky conditions: clear-sky, broken-clouds and overcast conditions. Two integrations, one per PBL parameterization, were carried out for every sky condition and season of the year and results were compared with observational data. Overall, the MM5 model, both using the Blackadar or MRF PBL parameterization, revealed to be a valid tool to estimate hourly values of solar radiation and temperature over the study area. The influence of the PBL parameterization on the model estimates was found to be more important for the solar radiation than for the temperature and highly dependent on the season and sky conditions. Particularly, a detailed analysis revealed that, during broken-clouds conditions, the ability of the model to reproduce hourly changes in the solar radiation strongly depends upon the selected PBL parameterization. Additionally, it was found that solar radiation RMSE values are about one order of magnitude higher during broken-clouds and overcast conditions compared to clear-sky conditions. For the temperature, the two PBL parameterizations provide very similar estimates. Only under overcast conditions and during the autumn, the MRF provides significantly better estimates

Adherence to Mediterranean Diet Pattern among Spanish Adults Attending a Medical Centre: Nondiabetic Subjects and Type 1 and 2 Diabetic Patients.

Objective. To identify adherence to Mediterranean diet among two groups of Spanish adults: diabetic patients and nondiabetic subjects. Methods. Adherence to Mediterranean diet was measured by a 14-item screener (scale: 0–14; =5: low, 6–9: moderate, and =10: high) in 351 volunteers. Results. Mean age was 50.97±12.58 in nondiabetics (n=154) and 59.50±13.34 in diabetics (n = 197). The whole sample scored 8.77 ± 1.82. Score was 9.19 ± 1.84 in nondiabetic females (n = 58) and 8.15 ± 1.79 in diabetic females (n = 85) (p = 0 003), due to lower consumption of olive oil (p = 0 005) and nuts (p = 0 000). Type 2 diabetic males (n = 79; 8.76 ± 1.88) consumed less olive oil than healthy males (n = 28; 9.36 ± 1.59) (p = 0 046). Up to 30-year-old nondiabetics scored lower than more than 60-year-old nondiabetics (8.40 ± 1.5 versus 9.74 ± 2.03; p = 0 047). The youngest ate less olive oil (p = 0 002) and more pastries (p = 0 007). Conclusions. The sample presented moderate adherence to Mediterranean diet in all subgroups. Scientific evidence about the benefits of Mediterranean diet, olive oil, and nuts supports the recommendation to increase consumption of olive oil and nuts in diabetic women and of daily olive oil in type 2 diabetic men, reducing consumption of red meat, butter, and pastries, and to promote Mediterranean diet among the youngest of the sample studie

Impact of Size, Secondary Structure, and Counterions on the Binding of Small Ribonucleic Acids to Layered Double Hydroxide Nanoparticles

Use of ribonucleic acid (RNA) interference to regulate protein expression has become an important research topic and gene therapy tool, and therefore, finding suitable vehicles for delivery of small RNAs into cells is of crucial importance. Layered double metal hydroxides such as hydrotalcite (HT) have shown great promise as nonviral vectors for transport of deoxyribose nucleic acid (DNA), proteins, and drugs into cells, but the adsorption of RNAs to these materials has been little explored. In this study, the binding of small RNAs with different lengths and levels of secondary structure to HT nanoparticles has been analyzed and compared to results obtained with small DNAs in concurrent experiments. Initial experiments established the spectrophotometric properties of HT in aqueous solutions and determined that HT particles could be readily sedimented with near 100% efficiencies. Use of RNA+HT cosedimentation experiments as well as electrophoretic mobility shift assays demonstrated strong adsorption of RNA 25mers to HT, with twofold greater binding of single-stranded RNAs relative to double-stranded molecules. Strong affinities were also observed with ssRNA and dsRNA 54mers and with more complex transfer RNA molecules. Competition binding and RNA displacement experiments indicated that RNA-HT associations were strong and were only modestly affected by the presence of high concentrations of inorganic anions

Role of the ecto-nucleotidases in the cooperative effect of adenosine and neuropeptide-S on locomotor activity in mice.

Abstract Activation of adenosine receptors modifies the action of classic neurotransmitters (i.e. dopamine, glutamate and acetylcholine) and other neuromodulators, like vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide S (NPS). Similarly to adenosine, NPS is involved in the regulation of stimulus and response to fear and arousal. Thus, the present study investigates the effects of NPS on locomotor activity in mice treated with or without α,β-methylene adenosine 5′-diphosphate (AOPCP), the inhibitor of ecto-5′-nucleotidase. Additionally, we evaluate the activity of ecto-5′-nucleotidase in brain slices of mice treated with or without NPS. Male adult CF-1 mice received i.c.v. NPS as 0.1 nmol injection with or without pre-treatment with 1 nmol α,β-methylene adenosine 5′-diphosphate (AOPCP), the selective inhibitor of ecto-5′-nucleotidase, to evaluate locomotor activity. In another set of experiments, mice received i.c.v. infusion of 0.1 nmol NPS to assay enzymatic activity in brain slices. The results demonstrated that the pre-treatment with AOPCP, which was inactive per se, prevented NPS-induced hyperlocomotion in mice. The dose of 0.1 nmol NPS was efficient to induce hyperlocomotion in animals during the observation period in the activity cage. Regarding enzymatic activity, i.c.v. NPS injection did not induce any significant alterations in ATP and AMP hydrolysis in striatum and hippocampus brain slices of mice. The present study shows that the hyperlocomotor effect of NPS depends on the ecto-5′-nucleotidase activity

Metformin reduces macrophage HIF1α-dependent proinflammatory signaling to restore brown adipocyte function in vitro

© 2021 The Authors.Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance. However, it remains largely unknown the signaling pathways involved and whether some cell types are particularly relevant for its beneficial effects. M1-activation of macrophages by bacterial lipopolysaccharide (LPS) promotes a paracrine activation of hypoxia-inducible factor-1α (HIF1α) in brown adipocytes which reduces insulin signaling and glucose uptake, as well as β-adrenergic sensitivity. Addition of metformin to M1-polarized macrophages blunted these signs of brown adipocyte dysfunction. At the molecular level, metformin inhibits an inflammatory program executed by HIF1α in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner. In obese mice, metformin reduced inflammatory features in brown adipose tissue (BAT) such as macrophage infiltration, proinflammatory signaling and gene expression, and restored the response to cold exposure. In conclusion, the impact of metformin on macrophages by suppressing a HIF1α-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and β-adrenergic responses in brown adipocytes.This work was funded by grants RTI2018-094052-B-100 (MCIN/AEI/10.13039/501100011033/FEDER) , S2017/BMD-3684 (Comunidad de Madrid, Spain), Fundación Ramón Areces (Spain) and CIBERdem (ISCIII) to A.M.V., grant S2010/BMD-2423 (Comunidad de Madrid, Spain) to M.J.O. and A.M.V., PID2019-106371RB-I00 (MCIN/ AEI /10.13039/501100011033/ FEDER) to J.A and PI16/00789 (ISCIII, Spain) to M.A.F.-M. We also acknowledge all members of AMV's laboratory for helpful discussions. M.F. and B.V were supported by Inserm, CNRS, Université de Paris, and Région Ile-de-France. We also acknowledge the EFSD Albert Reynolds travel grant fellowship to V.F

Oxygen Sensing in Drosophila: Multiple Isoforms of the Prolyl Hydroxylase Fatiga Have Different Capacity to Regulate HIFα/Sima

Background: The Hypoxia Inducible Factor (HIF) mediates cellular adaptations to low oxygen. Prolyl-4-hydroxylases are oxygen sensors that hydroxylate the HIF alpha-subunit, promoting its proteasomal degradation in normoxia. Three HIFprolyl hydroxylases, encoded by independent genes, PHD1, PHD2, and PHD3, occur in mammals. PHD2, the longest PHD isoform includes a MYND domain, whose biochemical function is unclear. PHD2 and PHD3 genes are induced in hypoxia to shut down HIF dependent transcription upon reoxygenation, while expression of PHD1 is oxygen-independent. The physiologic significance of the diversity of the PHD oxygen sensors is intriguing. Methodology and Principal Findings: We have analyzed the Drosophila PHD locus, fatiga, which encodes 3 isoforms, FgaA, FgaB and FgaC that are originated through a combination of alternative initiation of transcription and alternative splicing. FgaA includes a MYND domain and is homologous to PHD2, while FgaB and FgaC are shorter isoforms most similar to PHD3. Through a combination of genetic experiments in vivo and molecular analyses in cell culture, we show that fgaB but not fgaA is induced in hypoxia, in a Sima-dependent manner, through a HIF-Responsive Element localized in the first intron of fgaA. The regulatory capacity of FgaB is stronger than that of FgaA, as complete reversion of fga loss-of-function phenotypes is observed upon transgenic expression of the former, and only partial rescue occurs after expression of the latter. Conclusions and Significance: Diversity of PHD isoforms is a conserved feature in evolution. As in mammals, there are hypoxia-inducible and non-inducible Drosophila PHDs, and a fly isoform including a MYND domain co-exists with isoforms lacking this domain. Our results suggest that the isoform devoid of a MYND domain has stronger regulatory capacity than that including this domain.Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Centanin, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Dekanty, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Gene expression microarray analysis of early oxygen-induced retinopathy in the rat

Different inbred strains of rat differ in their susceptibility to oxygen-induced retinopathy (OIR), an animal model of human retinopathy of prematurity. We examined gene expression in Sprague–Dawley (susceptible) and Fischer 344 (resistant) neonatal rats after 3 days exposure to cyclic hyperoxia or room air, using Affymetrix rat Genearrays. False discovery rate analysis was used to identify differentially regulated genes. Such genes were then ranked by fold change and submitted to the online database, DAVID. The Sprague–Dawley list returned the term “response to hypoxia,” absent from the Fischer 344 output. Manual analysis indicated that many genes known to be upregulated by hypoxia-inducible factor-1α were downregulated by cyclic hyperoxia. Quantitative real-time RT-PCR analysis of Egln3, Bnip3, Slc16a3, and Hk2 confirmed the microarray results. We conclude that combined methodologies are required for adequate dissection of the pathophysiology of strain susceptibility to OIR in the rat