Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.     

Roles of Calcium Signaling in Gene Expression and Photosynthetic Acclimatization of Solanum lycopersicum Micro-Tom (MT) after Mechanical Damage

A momentary increase in cytoplasmic Ca²⁺ generates an oscillation responsible for the activation of proteins, such as calmodulin and kinases, which interact with reactive oxygen species (ROS) for the transmission of a stress signal. This study investigated the influence of variations in calcium concentrations on plant defense signaling and photosynthetic acclimatization after mechanical damage. Solanum lycopersicum Micro-Tom was grown with 0, 2 and 4 mM Ca²⁺, with and without mechanical damage. The expression of stress genes was evaluated, along with levels of antioxidant enzymes, hydrogen peroxide, lipid peroxidation, histochemistry, photosynthesis and dry mass of organs. The ROS production generated by mechanical damage was further enhanced by calcium-free conditions due to the inactivation of the oxygen evolution complex, contributing to an increase in reactive species. The results indicated that ROS affected mechanical damage signaling because calcium-free plants exhibited high levels of H₂O₂ and enhanced expression of kinase and RBOH1 genes, necessary conditions for an efficient response to stress. We conclude that the plants without calcium supply recognized mechanical damage but did not survive. The highest expression of the RBOH1 gene and the accumulation of H₂O₂ in these plants signaled cell death. Plants grown in the presence of calcium showed higher expression of SlCaM2 and control of H₂O₂ concentration, thus overcoming the stress caused by mechanical damage, with photosynthetic acclimatization and without damage to dry mass production.     

Study of the Ghrelin/LEAP-2 Ratio in Humans and Rats during Different Phases of Pregnancy

The Liver-Expressed Antimicrobial Peptide 2 (LEAP-2) has emerged as an endogenous GHS-R antagonist and blunts the orexigenic action of ghrelin. This study aimed to determine the Ghrelin/LEAP-2 ratio in humans and rats during pregnancy. In humans, we conducted a nested case-control study within an observational prospective cohort. Healthy and mild preeclamptic pregnant women were studied at each trimester of gestation and three months postpartum. In addition, a group of non-pregnant women was studied into the follicular and luteal phases of the menstrual cycle. Furthermore, Ghrelin/LEAP-2 ratio was investigated in non-pregnant rats and at different periods of rat pregnancy. Human and rat serum ghrelin and LEAP-2 levels were determined using the commercially available ELISA kits. The Ghrelin/LEAP-2 ratio peak around the second trimester of gestation in healthy pregnant women (p < 0.05). Additionally, there were no statistically significant differences in Ghrelin/LEAP-2 ratio between healthy and preeclamptic pregnant women at each trimester of gestation (p > 0.05). The Ghrelin/LEAP-2 ratio in pregnant rat reached the peak around mid-gestation with a similar pattern to the human pregnancy. LEAP-2 was visualized by immunohistochemistry in human term placenta and rat placentas on days 12, 16 and 21 of pregnancy. In conclusion, this study provides the first evidence of a Ghrelin/LEAP-2 ratio peak around the half-way point of pregnancy onwards during human and rat pregnancy, and it might be associated with increased rates of weight gain during pregnancy. Thus, this study suggests that LEAP-2 and Ghrelin/LEAP-2 ratio might play an important role in maternal physiology adaptation of weight gain during pregnancy.     

Advanced and Intelligent Control Techniques Applied to the Drive Control and Path Tracking Systems on a Robotic Wheelchair

This paper presents the theoretical support and experimental results of the application of advanced and intelligent control techniques to the drive control and trajectory tracking systems on a robotic wheelchair. The adaptive optimal control of the differential drive helps to improve the automatic guidance system's safety and comfort taking into consideration operating conditions such as load and distribution changes or motion actuator limitations. Furthermore, the incorporation of an optimal controller to minimize location errors and a fuzzy controller to adapt the linear velocity to the characteristics of the trajectory, provide the vehicle with a high degree of intelligence and autonomy, even when faced with obstacles. The global control solution implemented increases the features of the wheelchair for handicapped people, especially for those with a high degree of disability.     

Improving the performance and functionality of Mondrian open‐source OLAP systems

For a long time, the design of relational databases has focused on the optimization of atomic transactions (insert, select, update or delete). Currently, relational databases store tactical information of data warehouses, mainly for select‐like operations. However, the database paradigm has evolved, and nowadays on‐line analytical processing (OLAP) systems handle strategic information for further analysis. These systems enable fast, interactive and consistent information analysis of data warehouses, including shared calculations and allocations. OLAP and data warehouses jointly allow multidimensional data views, turning raw data into knowledge. OLAP allows ‘slice and dice’ navigation and a top‐down perspective of data hierarchies. In this paper, we describe our experience in the migration from a large relational database management system to an OLAP system on top of a relational layer (the data warehouse), and the resulting contributions in open‐source ROLAP optimization. Existing open‐source ROLAP technologies rely on summarized tables with materialized aggregate views to improve system performance (in terms of response time). The design and maintenance of those tables are cumbersome. Instead, we intensively exploit cache memory, where key data reside, yielding low response times. A cold start process brings summarized data from the relational database to cache memory, subsequently reducing the response time. We ensure concurrent access to the summarized data, as well as consistency when the relational database updates data. We also improve the OLAP functionality, by providing new features for automating the creation of calculated members. This makes it possible to define new measures on the fly using virtual dimensions, without re‐designing the multidimensional cube. We have chosen the XML/A de facto standard for service provision. Copyright © 2008 John Wiley & Sons, Ltd.     

Mucopolysaccharidoses: Cellular Consequences of Glycosaminoglycans Accumulation and Potential Targets

Mucopolysaccharidoses (MPSs) constitute a heterogeneous group of lysosomal storage disorders characterized by the lysosomal accumulation of glycosaminoglycans (GAGs). Although lysosomal dysfunction is mainly affected, several cellular organelles such as mitochondria, endoplasmic reticulum, Golgi apparatus, and their related process are also impaired, leading to the activation of pathophysiological cascades. While supplying missing enzymes is the mainstream for the treatment of MPS, including enzyme replacement therapy (ERT), hematopoietic stem cell transplantation (HSCT), or gene therapy (GT), the use of modulators available to restore affected organelles for recovering cell homeostasis may be a simultaneous approach. This review summarizes the current knowledge about the cellular consequences of the lysosomal GAGs accumulation and discusses the use of potential modulators that can reestablish normal cell function beyond ERT-, HSCT-, or GT-based alternatives.     

Integrated Computational Life Cycle Engineering — Application to the case of electric vehicles

Modelling and analysing lifecycle environmental impacts of product systems demands often specialized knowledge and is time-demanding. Product systems are typically defined by complex technical foreground systems and immersed in highly diverse contexts and background systems. Available software tools fail to streamline the modelling and analysis of this complexity, leading to extensive iterations or rough simplifications. The approach introduced in this paper supports the modelling of complex systems and their interactions with diverse backgrounds. This enables developing flexible and comprehensive environmental assessment tools. The applicability and advantages of the approach developed is demonstrated through its application for the environmental assessment of electric vehicles.     

Efficient code development for improving execution performance in high-performance computing centers

The Journal of Supercomputing - Thanks to high-performance computing (HPC), it is possible to solve all kinds of highly complex projects from multiple scientific disciplines that require...