DNA methylation in genes of longevity‐regulating pathways: association with obesity and metabolic complications

Aging is the main risk factor for most chronic diseases. Epigenetic mechanisms, such as DNA methylation (DNAm) plays a pivotal role in the regulation of physiological responses that can vary along lifespan. The aim of this research was to analyze the association between leukocyte DNAm in genes involved in longevity and the occurrence of obesity and related metabolic alterations in an adult population. Subjects from the MENA cohort (n=474) were categorized according to age () and the presence of metabolic alterations: increased waist circumference, hypercholesterolemia, insulin resistance, and metabolic syndrome. The methylation levels of 58 CpG sites located at genes involved in longevity‐regulating pathways were strongly correlated (FDR‐ adjusted< 0.0001) with BMI. Fifteen of them were differentially methylated (p<0.05) between younger and older subjects that exhibited at least one metabolic alteration. Six of these CpG sites, located at MTOR (cg08862778), ULK1 (cg07199894), ADCY6 (cg11658986), IGF1R (cg01284192), CREB5 (cg11301281), and RELA (cg08128650), were common to the metabolic traits, and CREB5, RELA, and ULK1 were statistically associated with age. In summary, leukocyte DNAm levels of several CpG sites located at genes involved in longevity‐ regulating pathways were associated with obesity and metabolic syndrome traits, suggesting a role of DNAm in aging‐related metabolic alterations

In situ synthesis of fluorescent silicon nanodots for determination of total carbohydrates in a paper microfluidic device combined with laser prepared graphene heater

We report a simple, rapid, low-resource and one-step method for formation of fluorescent silicon nanodots (SNDs) in a microfluidic paper-based analytical device (μPAD) incorporated in a reusable, portable and flexible heater for determination of total carbohydrates. The synthesis of SNDs is based on the redox reaction between (3-aminopropyl) triethoxysilane (APTS) reagent and carbohydrates, which act as a reducer. The graphene-based heater was fabricated by laser ablation of Kapton polyimide. Thereby, the developed system heat the μPAD during the synthesis of SNDs at 80 °C for 30 min. The blue emitting SNDs formed have an emission peak wavelength at 475 nm. We used a digital camera and smartphone for the quantitative analysis of total carbohydrates expressed such as index of glucose or fructose with grey scale value as the analytical parameter. Under the optimal conditions, the method has a low detection limit (0.80 μM for glucose and 0.51 μM for fructose, respectively), and a linear response (10–200 μM for glucose and 10–100 μM for fructose). The method has been applied to the determination of glucose in biological fluids (serum and urine samples). In addition, determination of total carbohydrates in commercial juices and teas have been carried outThis work was founded by Spanish “Ministerio de Economía y Competitividad” (Projects PID2019-103938RB-I00 and CTQ2017-86125-P) and Junta de Andalucía (Projects B-FQM-243-UGR18 and P18-RT-2961). The projects were partially supported by European Regional Development Funds (ERDF)

Aplicación de la metodologia de aula invertida 'Team Based Learning' en cinco assignaturas en la Facultad de Química a través de un proyecto de aprendizaje reflexivo/experiencial

La metodología de Aula Inversa "Team Based Learing" (TBL) se ha aplicado en 5 asignaturas en la Facultat de Química de la Universitat de Barcelona. El proyecto se ha desarrollado en un entorno reflexivo/experiencial en el que los profesores (10 en total)han actuado como profesores y observadores. Este funcionamiento les ha permitido adquirir una experiencia que facilitará la futura aplicación de la metodología TBL, la cual ha sido valorada positivamente por docentes y estudiantes

Epigenome-wide association study in peripheral white blood cells involving insulin resistance

Insulin resistance (IR) is a hallmark of type 2 diabetes, metabolic syndrome and cardiometabolic risk. An epigenetic phenomena such as DNA methylation might be involved in the onset and development of systemic IR. The aim of this study was to explore the genetic DNA methylation levels in peripheral white blood cells with the objective of identifying epigenetic signatures associated with IR measured by the Homeostatic Model Assessment of IR (HOMA-IR) following an epigenome-wide association study approach. DNA methylation levels were assessed using Infinium Methylation Assay (Illumina), and were associated with HOMA-IR values of participants from the Methyl Epigenome Network Association (MENA) project, finding statistical associations for at least 798 CpGs. A stringent statistical analysis revealed that 478 of them showed a differential methylation pattern between individuals with HOMA-IR ≤ 3 and > 3. ROC curves of top four CpGs out of 478 allowed differentiating individuals between both groups (AUC≈0.88). This study demonstrated the association between DNA methylation in some specific CpGs and HOMA-IR values that will help to the understanding and in the development of new strategies for personalized approaches to predict and prevent IR-associated diseases

Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

Background: Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients. Methods: Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC. Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight. Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters. Findings: First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%). Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy). Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement. Interpretation: Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects. Funding: None.We would like to acknowledge the Instituto de Salud Carlos III (ISCIII) through the project “RD16/0011: Red de Terapia Celular”, from the sub-program RETICS, integrated in the “Plan Estatal de I+D+I 2013-2016” and co-financed by the European Regional Development Fund “A way to make Europe”, groups RD16/0011/0001, -/0002, -/005, -/0013, -/0015, -/0029), the Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Spain and AvanCell-CM (Red de Investigación de Terapia Celular de la Comunidad de Madrid, Spain), for supporting some personnel and networking activities

Finite Horizon Nonlinear Energy Optimizing Control in a Force Augmenting Hybrid Exoskeleton for the Elbow Joint

International audienc

Comparative Analysis of a Family of Sliding Mode Observers under Real-Time Conditions for the Monitoring in the Bioethanol Production

Online monitoring of fermentation processes is a necessary task to determine concentrations of key biochemical compounds, diagnose faults in process operations, and implement feedback controllers. However, obtaining the signals of all-important variables in a real process is a task that may be difficult and expensive due to the lack of adequate sensors, or simply because some variables cannot be directly measured. From the above, a model-based approach such as state observers may be a viable alternative to solve the estimation problem. This work shows a comparative analysis of the real-time performance of a family of sliding-mode observers for reconstructing key variables in a batch bioreactor for fermentative ethanol production. These observers were selected for their robust performance under model uncertainties and finite-time estimation convergence. The selected sliding-mode observers were the first-order sliding mode observer, the proportional sliding mode observer, and the high-order sliding mode observer. For estimation purposes, a power law kinetic model for ethanol production by Saccharomyces cerevisiae was performed. A hybrid methodology allows the kinetic parameters to be adjusted, and an approach based on inference diagrams allows the observability of the model to be determined. The experimental results reported here show that the observers under analysis were robust to modeling errors and measurement noise. Moreover, the proportional sliding-mode observer was the algorithm that exhibited the best performance

Photosynthetic characteristics of iron chlorotic pear (Pyrus commuais L.)

8 Pags. Journal of Plant Nutrition Special Issue: Iron NutritionThe photosystem II photochemical efficiency of pear leaves was found to decrease during the day. This occurred both in iron sufficient and deficient leaves. Decreases in the photosystem II photochemical efficiency depended both on the time of sampling and on the relaxation time in the dark before fluorescence measurements were made. Decreases in the efficiency of photosystem II were accompanied by a relative increase in the part of variable fluorescence leading to the “I”; point in the Kautsky induction curve. When left in the dark, control and moderately iron‐deficient pear leaves recovered to show a good efficiency of photosystem II photochemistry. These results suggest that some type of easily reversible photoinhibition occurred in pear leaves under field conditions. However, when chlorophyll decreased below a threshold level, iron deficiency caused major decreases in the efficiency of photosystem II photochemistry and relative increases in the part of variable fluorescence leading to the “I”; point in the chlorophyll fluorescence induction curve, which were irreversible in the dark.Peer reviewe

Associations between olfactory pathway gene methylation marks, obesity features and dietary intakes

Background: Olfaction is an important sense influencing food preferences, appetite, and eating behaviors. This hypothesis-driven study aimed to assess associations between olfactory pathway gene methylation signatures, obesity features, and dietary intakes. Methods: A nutriepigenomic analysis was conducted in 474 adults from the Methyl Epigenome Network Association (MENA) project. Anthropometric measurements, clinical data, and serum metabolic profiles of the study population were obtained from structured databases of the MENA cohorts. Habitual dietary intake was assessed using a validated semiquantitative food frequency questionnaire. DNA methylation was measured in circulating white blood cells by microarray (Infinium Human Methylation 450 K BeadChips). FDR values (p < 0.0001) were used to select those CpGs that showed the best correlation with body mass index (BMI) and waist circumference (WC). Pathway analyses involving the characterization of genes involved in the olfactory transduction system were performed using KEGG and pathDIP reference databases. Results: Overall, 15 CpG sites at olfactory pathway genes were associated with BMI (p < 0.0001) and WC (p < 0.0001) after adjustments for potential confounding factors. Together, methylation levels at the15 CpG sites accounted for 22% and 20% of the variability in BMI and WC (r 2 = 0.219, p < 0.001, and r 2 = 0.204, p < 0.001, respectively). These genes encompassed olfactory receptors (OR4D2, OR51A7, OR2T34, and OR2Y1) and several downstream signaling molecules (SLC8A1, ANO2, PDE2A, CALML3, GNG7, CALML6, PRKG1, and CAMK2D), which significantly regulated odor detection and signal transduction processes within the complete olfactory cascade, as revealed by pathway enrichment analyses (p = 1.94 × 10–10). Moreover, OR4D2 and OR2Y1 gene methylation patterns strongly correlated with daily intakes of total energy (p < 0.0001), carbohydrates (p < 0.0001), protein (p < 0.0001), and fat (p < 0.0001). Conclusions: The results of this study suggest novel relationships between olfactory pathway gene methylation signatures, obesity indices, and dietary intakes