p66Shc signaling and autophagy impact on C2C12 myoblast differentiation during senescence.

During aging, muscle regenerative capacities decline, which is concomitant with the loss of satellite cells that enter in a state of irreversible senescence. However, what mechanisms are involved in myogenic senescence and differentiation are largely unknown. Here, we showed that early-passage or "young" C2C12 myoblasts activated the redox-sensitive p66Shc signaling pathway, exhibited a strong antioxidant protection and a bioenergetic profile relying predominantly on OXPHOS, responses that decrease progressively during differentiation. Furthermore, autophagy was increased in myotubes. Otherwise, late-passage or "senescent" myoblasts led to a highly metabolic profile, relying on both OXPHOS and glycolysis, that may be influenced by the loss of SQSTM1/p62 which tightly regulates the metabolic shift from aerobic glycolysis to OXPHOS. Furthermore, during differentiation of late-passage C2C12 cells, both p66Shc signaling and autophagy were impaired and this coincides with reduced myogenic capacity. Our findings recognized that the lack of p66Shc compromises the proliferation and the onset of the differentiation of C2C12 myoblasts. Moreover, the Atg7 silencing favored myoblasts growth, whereas interfered in the viability of differentiated myotubes. Then, our work demonstrates that the p66Shc signaling pathway, which highly influences cellular metabolic status and oxidative environment, is critical for the myogenic commitment and differentiation of C2C12 cells. Our findings also support that autophagy is essential for the metabolic switch observed during the differentiation of C2C12 myoblasts, confirming how its regulation determines cell fate. The regulatory roles of p66Shc and autophagy mechanisms on myogenesis require future attention as possible tools that could predict and measure the aging-related state of frailty and disability.

AI-IoT Low-Cost Pollution-Monitoring Sensor Network to Assist Citizens with Respiratory Problems.

The proliferation and great variety of low-cost air quality (AQ) sensors, combined with their flexibility and energy efficiency, gives an opportunity to integrate them into Wireless Sensor Networks (WSN). However, with these sensors, AQ monitoring poses a significant challenge, as the data collection and analysis process is complex and prone to errors. Although these sensors do not meet the performance requirements for reference regulatory-equivalent monitoring, they can provide informative measurements and more if we can adjust and add further processing to their raw measurements. Therefore, the integration of these sensors aims to facilitate real-time monitoring and achieve a higher spatial and temporal sampling density, particularly in urban areas, where there is a strong interest in providing AQ surveillance services since there is an increase in respiratory/allergic issues among the population. Leveraging a network of low-cost sensors, supported by 5G communications in combination with Artificial Intelligence (AI) techniques (using Convolutional and Deep Neural Networks (CNN and DNN)) to predict 24-h-ahead readings is the goal of this article in order to be able to provide early warnings to the populations of hazards areas. We have evaluated four different neural network architectures: Multi-Linear prediction (with a dense Multi-Linear Neural Network (NN)), Multi-Dense network prediction, Multi-Convolutional network prediction, and Multi-Long Short-Term Memory (LSTM) network prediction. To perform the training of the prediction of the readings, we have prepared a significant dataset that is analyzed and processed for training and testing, achieving an estimation error for most of the predicted parameters of around 7.2% on average, with the best option being the Multi-LSTM network in the forthcoming 24 h. It is worth mentioning that some pollutants achieved lower estimation errors, such as CO2 with 0.1%, PM10 with 2.4% (as well as PM2.5 and PM1.0), and NO2 with 6.7%.

Melatonin Alleviates the Impairment of Muscle Bioenergetics and Protein Quality Control Systems in Leptin-Deficiency-Induced Obesity.

Leptin is critically compromised in the major common forms of obesity. Skeletal muscle is the main effector tissue for energy modification that occurs as a result of the effect of endocrine axes, such as leptin signaling. Our study was carried out using skeletal muscle from a leptin-deficient animal model, in order to ascertain the importance of this hormone and to identify the major skeletal muscle mechanisms affected. We also examined the therapeutic role of melatonin against leptin-induced muscle wasting. Here, we report that leptin deficiency stimulates fatty acid ß-oxidation, which results in mitochondrial uncoupling and the suppression of mitochondrial oxidative damage; however, it increases cytosolic oxidative damage. Thus, different nutrient-sensing pathways are disrupted, impairing proteostasis and promoting lipid anabolism, which induces myofiber degeneration and drives oxidative type I fiber conversion. Melatonin treatment plays a significant role in reducing cellular oxidative damage and regulating energy homeostasis and fuel utilization. Melatonin is able to improve both glucose and mitochondrial metabolism and partially restore proteostasis. Taken together, our study demonstrates melatonin to be a decisive mitochondrial function-fate regulator in skeletal muscle, with implications for resembling physiological energy requirements and targeting glycolytic type II fiber recovery.

Cell interactome in sarcopenia during aging.

BACKGROUND: The diversity between the muscle cellular interactome of dependent and independent elderly people is based on the interrelationships established between different cellular mechanisms, and alteration of this balance modulates cellular activity in muscle tissue with important functional implications. METHODS: Thirty patients (85 ± 8 years old, 23% female) scheduled to undergo hip fracture surgery participated in this study. During the surgical procedures, skeletal muscle tissue was obtained from the Vastus lateralis. Two groups of participants were studied based on their Barthel index: 15 functional-independent individuals (100-90) and 15 severely functional-dependent individuals (40-0). The expression of proteins from the most important cellular mechanisms was studied by western blot. RESULTS: Compared with independent elderly patients, dependent elderly showed an abrupt decrease in the capacity of protein synthesis; this decrease was only partially compensated for at the response to unfolded or misfolded proteins (UPR) level due to the increase in IRE1 (P < 0.001) and ATF6 (P < 0.05), which block autophagy, an essential mechanism for cell survival, by decreasing the expression of Beclin-1, LC3, and p62 (P < 0.001) and the antioxidant response. This lead to increased oxidative damage to lipids (P < 0.001) and that damage was directly associated with the mitochondrial impairment induced by the significant decreases in the I, III, IV, and V mitochondrial complexes (P < 0.01), which drastically reduced the energy capacity of the cell. The essential cellular mechanisms were generally impaired and the triggering of apoptosis was induced, as shown by the significantly elevated levels of most proapoptotic proteins (P < 0.05) and caspase-3/7 (P < 0.001) in dependents. The death of highly damaged cells is not detrimental to organs as long as the regenerative capacity remains unaltered, but in the dependent patients, this ability was also significantly altered, which was revealed by the reduction in the myogenic regulatory factors and satellite cell marker (P < 0.001), and the increase in myostatin (P < 0.01). Due to the severely disturbed cell interactome, the muscle contractile capacity showed significant damage. CONCLUSIONS: Functionally dependent patients exhibited severe alterations in their cellular interactome at the muscle level. Cell apoptosis was caused by a decrease in successful protein synthesis, to which the cellular control systems did not respond adequately; autophagy was simultaneously blocked, the mitochondrion malfunctioned, and as the essential recovery mechanisms failed, these cells could not be replaced, resulting in the muscle being condemned to a loss of mass and functionality.

Application of Radio Environment Map Reconstruction Techniques to Platoon-based Cellular V2X Communications.

Vehicle platoons involve groups of vehicles travelling together at a constant inter-vehicle distance, with different common benefits such as increasing road efficiency and fuel saving. Vehicle platooning requires highly reliable wireless communications to keep the group structure and carry out coordinated maneuvers in a safe manner. Focusing on infrastructure-assisted cellular vehicle to anything (V2X) communications, the amount of control information to be exchanged between each platoon vehicle and the base station is a critical factor affecting the communication latency. This paper exploits the particular structure and characteristics of platooning to decrease the control information exchange necessary for the channel acquisition stage. More precisely, a scheme based on radio environment map (REM) reconstruction is proposed, where geo-localized received power values are available at only a subset of platoon vehicles, while large-scale channel parameters estimates for the rest of platoon members are provided through the application of spatial Ordinary Kriging (OK) interpolation. Distinctive features of the vehicle platooning use case are explored, such as the optimal patterns of vehicles within the platoon with available REM values for improving the quality of the reconstruction, the need for an accurate semivariogram modeling in OK, or the communication cost when establishing a centralized or a distributed architecture for achieving REM reconstruction. The evaluation results show that OK is able to reconstruct the REM in the platoon with acceptable mean squared estimation error, while reducing the control information for REM acquisition in up to 64% in the best-case scenario.

Overweight in the Elderly Induces a Switch in Energy Metabolism that Undermines Muscle Integrity.

Aging is characterized by a progressive loss of skeletal muscle mass and function (sarcopenia). Obesity exacerbates age-related decline and lead to frailty. Skeletal muscle fat infiltration increases with aging and seems to be crucial for the progression of sarcopenia. Additionally, skeletal muscle plasticity modulates metabolic adaptation to different pathophysiological situations. Thus, cellular bioenergetics and mitochondrial profile were studied in the skeletal muscle of overweight aged people without reaching obesity to prevent this extreme situation. Overweight aged muscle lacked ATP production, as indicated by defects in the phosphagen system, glycolysis and especially mostly by oxidative phosphorylation metabolic pathway. Overweight subjects exhibited an inhibition of mitophagy that was linked to an increase in mitochondrial biogenesis that underlies the accumulation of dysfunctional mitochondria and encourages the onset of sarcopenia. As a strategy to maintain cellular homeostasis, overweight subjects experienced a metabolic switch from oxidative to lactic acid fermentation metabolism, which allows continued ATP production under mitochondrial dysfunction, but without reaching physiological aged basal levels. This ATP depletion induced early signs of impaired contractile function and a decline in skeletal muscle structural integrity, evidenced by lower levels of filamin C. Our findings reveal the main effector pathways at an early stage of obesity and highlight the importance of mitochondrial metabolism in overweight and obese individuals. Exploiting mitochondrial profiles for therapeutic purposes in humans is an ambitious strategy for treating muscle impairment diseases.

Spatio-Temporal Analysis of Urban Acoustic Environments with Binaural Psycho-Acoustical Considerations for IoT-Based Applications.

Sound pleasantness or annoyance perceived in urban soundscapes is a major concern in environmental acoustics. Binaural psychoacoustic parameters are helpful to describe generic acoustic environments, as it is stated within the ISO 12913 framework. In this paper, the application of a Wireless Acoustic Sensor Network (WASN) to evaluate the spatial distribution and the evolution of urban acoustic environments is described. Two experiments are presented using an indoor and an outdoor deployment of a WASN with several nodes using an Internet of Things (IoT) environment to collect audio data and calculate meaningful parameters such as the sound pressure level, binaural loudness and binaural sharpness. A chunk of audio is recorded in each node periodically with a microphone array and the binaural rendering is conducted by exploiting the estimated directional characteristics of the incoming sound by means of DOA estimation. Each node computes the parameters in a different location and sends the values to a cloud-based broker structure that allows spatial statistical analysis through Kriging techniques. A cross-validation analysis is also performed to confirm the usefulness of the proposed system.

Optimizing the MAC Protocol in Localization Systems Based on IEEE 802.15.4 Networks.

Radio frequency signals are commonly used in the development of indoor localization systems. The infrastructure of these systems includes some beacons placed at known positions that exchange radio packets with users to be located. When the system is implemented using wireless sensor networks, the wireless transceivers integrated in the network motes are usually based on the IEEE 802.15.4 standard. But, the CSMA-CA, which is the basis for the medium access protocols in this category of communication systems, is not suitable when several users want to exchange bursts of radio packets with the same beacon to acquire the radio signal strength indicator (RSSI) values needed in the location process. Therefore, new protocols are necessary to avoid the packet collisions that appear when multiple users try to communicate with the same beacons. On the other hand, the RSSI sampling process should be carried out very quickly because some systems cannot tolerate a large delay in the location process. This is even more important when the RSSI sampling process includes measures with different signal power levels or frequency channels. The principal objective of this work is to speed up the RSSI sampling process in indoor localization systems. To achieve this objective, the main contribution is the proposal of a new MAC protocol that eliminates the medium access contention periods and decreases the number of packet collisions to accelerate the RSSI collection process. Moreover, the protocol increases the overall network throughput taking advantage of the frequency channel diversity. The presented results show the suitability of this protocol for reducing the RSSI gathering delay and increasing the network throughput in simulated and real environments.

Overweight in elderly people induces impaired autophagy in skeletal muscle.

Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases.

Practical Considerations in the Implementation of Collaborative Beamforming on Wireless Sensor Networks.

Wireless Sensor Networks (WSNs) are composed of spatially distributed autonomous sensor devices, named motes. These motes have their own power supply, processing unit, sensors and wireless communications However with many constraints, such as limited energy, bandwidth and computational capabilities. In these networks, at least one mote called a sink, acts as a gateway to connect with other networks. These sensor networks run monitoring applications and then the data gathered by these motes needs to be retrieved by the sink. When this sink is located in the far field, there have been many proposals in the literature based on Collaborative Beamforming (CB), also known as Distributed or Cooperative Beamforming, for these long range communications to reach the sink. In this paper, we conduct a thorough study of the related work and analyze the requirements to do CB. In order to implement these communications in real scenarios, we will consider if these requirements and the assumptions made are feasible from the point of view of commercial motes and their constraints. In addition, we will go a step further and will consider different alternatives, by relaxing these requirements, trying to find feasible assumptions to carry out these types of communications with commercial motes. This research considers the nonavailability of a central clock that synchronizes all motes in the WSN, and all motes have identical hardware. This is a feasibility study to do CB on WSN, using a simulated scenario with randomized delays obtained from experimental data from commercial motes.

RF-Based Location Using Interpolation Functions to Reduce Fingerprint Mapping.

Indoor RF-based localization using fingerprint mapping requires an initial training step, which represents a time consuming process. This location methodology needs a database conformed with RSSI (Radio Signal Strength Indicator) measures from the communication transceivers taken at specific locations within the localization area. But, the real world localization environment is dynamic and it is necessary to rebuild the fingerprint database when some environmental changes are made. This paper explores the use of different interpolation functions to complete the fingerprint mapping needed to achieve the sought accuracy, thereby reducing the effort in the training step. Also, different distributions of test maps and reference points have been evaluated, showing the validity of this proposal and necessary trade-offs. Results reported show that the same or similar localization accuracy can be achieved even when only 50% of the initial fingerprint reference points are taken.

Melatonin administration decreases adipogenesis in the liver of ob/ob mice through autophagy modulation.

Despite efforts to curb the incidence of obesity and its comorbidities, this condition remains the fifth leading cause of death worldwide. To identify ways to reduce this global effect, we investigated the actions of daily melatonin administration on oxidative stress parameters and autophagic processes as a possible treatment of obesity in ob/ob mice. The involvement of melatonin in many physiological functions, such as the regulation of seasonal body weight variation, glucose uptake, or adiposity, and the role of this indoleamine as an essential antioxidant, has become the focus of numerous anti-obesity studies. Here, we examined the oxidative status in the livers of obese melatonin-treated and untreated mice, observing a decrease in the oxidative stress levels through elevated catalase activity. ROS-mediated autophagy was downregulated in the liver of melatonin-treated animals and was accompanied by significant accumulation of p62. Autophagy is closely associated with adipogenesis; in this study, we report that melatonin-treated obese mice also showed reduced adiposity, as demonstrated by diminished body weight and reduced peroxisome proliferator-activated receptor gamma expression. Based on these factors, it is reasonable to assume that oxidative stress and autophagy play important roles in obesity, and therefore, melatonin could be an interesting target molecule for the development of a potential therapeutic agent to curb body weight.

Chronic inflammation as predictor of 1-year hospitalization and mortality in elderly population.

BACKGROUND: Systemic low-grade inflammation is thought to be associated with an increased risk of adverse clinical outcomes in elderly population. We tested this notion with the goal of identifying useful potential biomarkers of 1-year hospitalization and mortality in the elderly population. DESIGN: A total of 120 institutionalized older subjects were enrolled as participants in this study, including 90 women and 30 men (ranging in age from 68 to 105 years), selected from Santa Teresa nursing home (Oviedo, Spain). We studied functional status, morbidity, socio-demographic characteristics and several inflammation and inflammation-related markers. RESULTS: The study included 95 non-hospitalized participants and 23 participants with at least one hospitalization during 1 year (19% of subjects). The study also included 100 survivors and 19 participants who died during the 1-year study (16% of subjects). In logistic regression models adjusted by age, sex, anti-inflammatory drug use and morbid conditions, high levels of interleukin 1 receptor antagonist (IL-1ra) and red blood cell distribution width (RDW) were associated with hospitalization and death at 1 year. Elevated levels of tumour necrosis factor α (TNF-α) were also associated with an increased risk of death at 1 year after adjusting for the same potential confounders. Multivariate logistic regression models showed that elevated serum levels of IL-1ra were intimately associated with 1-year subsequent hospitalization and mortality in aged subjects after adjusting for age, sex, anti-inflammatory drug use and morbid conditions. CONCLUSIONS: Current data suggest that IL-1ra is a predictor of 1-year hospitalization and mortality in the elderly population.

Power consumption analysis of operating systems for wireless sensor networks.

In this paper four wireless sensor network operating systems are compared in terms of power consumption. The analysis takes into account the most common operating systems--TinyOS v1.0, TinyOS v2.0, Mantis and Contiki--running on Tmote Sky and MICAz devices. With the objective of ensuring a fair evaluation, a benchmark composed of four applications has been developed, covering the most typical tasks that a Wireless Sensor Network performs. The results show the instant and average current consumption of the devices during the execution of these applications. The experimental measurements provide a good insight into the power mode in which the device components are running at every moment, and they can be used to compare the performance of different operating systems executing the same tasks.