RThybrid: A standardized and open-source real-time software model library for experimental neuroscience

Closed-loop technologies provide novel ways of online observation, control and bidirectional interaction with the nervous system, which help to study complex non-linear and partially observable neural dynamics. These protocols are often difficult to implement due to the temporal precision required when interacting with biological components, which in many cases can only be achieved using real-time technology. In this paper we introduce RTHybrid (www.github.com/GNB-UAM/RTHybrid), a free and open-source software that includes a neuron and synapse model library to build hybrid circuits with living neurons in a wide variety of experimental contexts. In an effort to encourage the standardization of real-time software technology in neuroscience research, we compared different open-source real-time operating system patches, RTAI, Xenomai 3 and Preempt-RT, according to their performance and usability. RTHybrid has been developed to run over Linux operating systems supporting both Xenomai 3 and Preempt-RT real-time patches, and thus allowing an easy implementation in any laboratory. We report a set of validation tests and latency benchmarks for the construction of hybrid circuits using this library. With this work we want to promote the dissemination of standardized, user-friendly and open-source software tools developed for open- and closed-loop experimental neuroscience.This work was supported by MINECO/FEDER DPI2015-65833-P, TIN2017-84452-R and ONRG grant N62909-14-1-N27

Determination of Cr, Cd, Sn, and Pb in Selected Herbal Products Available in Philippine Markets

The growing popularity of herbal products in the Philippines makes it imperative to monitor and ensure safety of consumers from metal contaminants. In this study, trace concentrations of Cr, Cd, Sn, and Pb in herbal products were simultaneously measured using a microwaveassisted digestion as sample pre-treatment and inductively coupled plasma mass spectrometry (ICP-MS) for elemental detection. Using the optimized method, recoveries of ERM CD281, the primary cer t i f ied reference material (CRM) used, were found to be between 80-89%, and the method detection limits (MDL) for Cr, Cd, Sn, and Pb were 0.15, 0.07, 0.3, and 0.14 μg/L, respectively. The linear ranges for Cr and other elements (Cd, Sn, and Pb) were 0.01-500 and 0.01-50 μg/L, respectively. All correlation coeff icients were 0.9999 or better. Most of the products tested had measurable trace metal concentrations, which were below the suggested maximum limits in herbal products. However, one product derived from mangosteen exceeded the limit for Cd (0.42 mg/kg). Subsequent analysis of metal content in tea infusions showed that only a small fraction of metals may leach out, suggesting that consumption of tea infusions pose lesser risks. The order of abundance of metals found in herbal products was Cr>Pb>Cd>Sn. The variability of metal concentrations in herbal products underlines the fact that many plant ingredients are susceptible to contamination, and quality control during processing must be improved to minimize the possibility of contamination. The results of this study suggest that vigilant monitoring of herbal products is imperative to avoid exposure to trace metal contamination

The role of heart rate on the associations between body composition and heart rate variability in children with overweight/obesity : the ActiveBrains project

Background: Heart rate variability (HRV) is negatively associated with body mass index and adiposity in several populations. However, less information is available about this association in children with overweight and obesity, especially severe/morbid obesity, taking into consideration the dependence of HRV on heart rate (HR). Objectives: (1) to examine associations between body composition measures and HRV, (2) to study differences in HRV between children with overweight and severe/morbid obesity; and (3) to test whether relationships and differences tested in objectives 1 and 2, respectively are explained by the dependency of HRV on HR. Methods: A total of 107 children with overweight/obesity (58% boys, 10.03 +/- 1.13 years) participated in this study. Body composition measures were evaluated by Dual-energy X-ray absorptiometry (DXA). HRV parameters were measured with Polar RS800CXR (R). Results: Body composition measures were negatively associated with HRV indicators of parasympathetic activity (beta values ranging from -0.207 to -0.307, all p 0.05). Conclusion: All associations between adiposity/obesity and HRV could be explained by HR, suggesting a key confounding role of HR in HRV studies in children with weight disturbances

Inflammatory biomarkers and brain health indicators in children with overweight and obesity: The ActiveBrains project

INTRODUCTION: Chronic inflammation plays an important role on the pathogenesis of several cardiovascular and metabolic diseases, as well as on brain function and behaviour. The aim of the present study was to examine the associations between inflammatory biomarkers and a wide range of brain health indicators (i.e., academic performance, executive function, behavioural and emotional functioning, and brain volume) in children with overweight/obesity. METHODS: A total of 107 children (10.0 ± 1.1 years, 41% girls) from the ActiveBrains project were included in the analysis. Five inflammatory biomarkers were analysed in plasma: white blood cell (WBC) count, interleukin-6 (IL-6), interleukin-1beta, tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). Academic performance was assessed by Woodcock-Munoz Tests of Achievement. Executive function was assessed through the Design Fluency Test for cognitive flexibility, the Stroop test for cognitive inhibition, and the Delayed Non-Match-to-Sample task for working memory. Behavioural and emotional functioning was evaluated through the Behavior Assessment System for Children (BASC) questionnaire. Total and regional brain volume was assessed by magnetic resonance imaging. RESULTS: IL-6 was inversely associated with adaptive skills (beta = -0.228; p = 0.030), while TNF-alpha was related to mathematics (beta = -0.198; p = 0.034). In addition, CRP was positively associated with externalizing (beta = 0.246; p = 0.046) and internalizing problems (beta = 0.234; p = 0.039), as well as the behavioural symptoms index (beta = 0.236; p = 0.047). However, these significant associations disappeared after multiple comparisons correction. Inflammatory biomarkers were not associated with executive function and total brain volumes. Regarding regional brain analyses, WBC was positively associated with gray matter volume in the left middle temporal gyrus (beta = 0.387; p < 0.001, k = 44), and CRP was positively associated with gray matter volume in the right superior temporal gyrus (beta = 0.439; p < 0.001, k = 29). Additionally, when adjusting by total brain volume, CRP was positively associated with gray matter volume in the right supplementary motor cortex (beta = 0.453; p < 0.001, k = 51). Moreover, both, IL-6 (beta = 0.366; p < 0.001, k = 81) and TNF-alpha (beta = 0.368; p < 0.001, k = 62) were positively associated with white matter volume around the right inferior frontal gyrus pars opercularis, while CRP was inversely associated with white matter volume around the left superior frontal gyrus (beta = -0.482; p < 0.001, k = 82). After adjusting by total brain volume, CRP was also inversely associated with white matter volume in 3 additional clusters (beta ranging from -0.473 to -0.404; p < 0.001, k = 87). CONCLUSIONS: Inflammation was slightly associated with brain health (i.e., academic performance, behavioural and emotional functioning and regional brain volume) in children with overweight or obesity. Further larger longitudinal and interventional studies are warranted to elucidate the short-term and long-term effect of systemic low-grade inflammation on children's brain health

Automatized offline and online exploration to achieve a target dynamics in biohybrid neural circuits built with living and model neurons

Biohybrid circuits of interacting living and model neurons are an advantageous means to study neural dynamics and to assess the role of specific neuron and network properties in the nervous system. Hybrid networks are also a necessary step to build effective artificial intelligence and brain hybridization. In this work, we deal with the automatized online and offline adaptation, exploration and parameter mapping to achieve a target dynamics in hybrid circuits and, in particular, those that yield dynamical invariants between living and model neurons. We address dynamical invariants that form robust cycle-by-cycle relationships between the intervals that build neural sequences from such interaction. Our methodology first attains automated adaptation of model neurons to work in the same amplitude regime and time scale of living neurons. Then, we address the automatized exploration and mapping of the synapse parameter space that lead to a specific dynamical invariant target. Our approach uses multiple configurations and parallel computing from electrophysiological recordings of living neurons to build full mappings, and genetic algorithms to achieve an instance of the target dynamics for the hybrid circuit in a short time. We illustrate and validate such strategy in the context of the study of functional sequences in neural rhythms, which can be easily generalized for any variety of hybrid circuit configuration. This approach facilitates both the building of hybrid circuits and the accomplishment of their scientific goalThis research was supported by grants AEI/FEDER PID2021-122347NB-100, PGC2018-095895-B-I00, and PID2020- 114867RB-I00 (funded by MCIN/AEI/10.13039/501100011033 and ERDF - "A way of making Europe”

The effects of an exercise intervention on neuroelectric activity and executive function in children with overweight/obesity:The ActiveBrains randomized controlled trial

Objective: To investigate whether a 20-week aerobic and resistance exercise program induces changes in brain current density underlying working memory and inhibitory control in children with overweight/obesity. Methods: A total of 67 children (10.00 ± 1.10 years) were randomized into an exercise or control group. Electroencephalography (EEG)-based current density (μA/mm2) was estimated using standardized low-resolution brain electromagnetic tomography (sLORETA) during a working memory task (Delayed non-matched-to-sample task, DNMS) and inhibitory control task (Modified flanker task, MFT). In DNMS, participants had to memorize four stimuli (Pokemons) and then select between two of them, one of which had not been previously shown. In MFT, participants had to indicate whether the centered cow (i.e., target) of five faced the right or left. Results: The exercise group had significantly greater increases in brain activation in comparison with the control group during the encoding phase of DNMS, particularly during retention of second stimuli in temporal and frontal areas (peak t = from 3.4 to 3.8, cluster size [k] = from 11 to 39), during the retention of the third stimuli in frontal areas (peak t = from 3.7 to 3.9, k = from 15 to 26), and during the retention of the fourth stimuli in temporal and occipital areas (peak t = from 2.7 to 4.3, k = from 13 to 101). In MFT, the exercise group presented a lower current density change in the middle frontal gyrus (peak t = −4.1, k = 5). No significant change was observed between groups for behavioral performance (p ≥ 0.05). Conclusion: A 20-week exercise program modulates brain activity which might provide a positive influence on working memory and inhibitory control in children with overweight/obesity.</p

RNA-seq profiling of Fugacium kawagutii reveals strong responses in metabolic processes and symbiosis potential to deficiencies of iron and other trace metals

Abstract(#br)A healthy symbiotic relationship between corals and Symbiodiniaceae relies on suitable temperature and adequate nutrients including trace metals. Besides global warming, trace metal deficiency has been shown to cause coral bleaching, a phenomenon responsible for extensive coral reef degradation around the world. How trace metal deficiency impacts Symbiodiniaceae and coral symbiosis is poorly understood, however. In this study, we applied RNA-seq to investigate how Fugacium kawagutii responds to the deficiency of five trace metals (Fe 2+ , Zn 2+ , Cu 2+ , Mn 2+ , Ni 2+ ). We identified 685 to 2805 differentially expressed genes (DEGs) from these trace metal deficiency conditions, among which 372 were commonly regulated by all the five trace metals and were significantly enriched in energy metabolism (e.g. fatty acid synthesis). Furthermore, genes associated with extracellular matrix (ECM), cell surface structure and cell adhesion were impacted, suggesting that the ability of recognition and adhesion of F. kawagutii may be altered by trace metal deficiencies. In addition, among the five metals, Fe 2+ deficiency exhibited the strongest influence, with Fe-rich redox elements and many antioxidant synthesis genes being markedly down-regulated, indicative of adaptive reduction of Fe demand but a compromised ability to combat oxidative stress. Overall, deficiency of trace metals (especially Fe) seems to repress growth and ability of ROS scavenging, elevate energy metabolism and innate immunity, and alter cell adhesion capability, with implications in symbiosis disruption and coral bleaching

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

OBJECTIVE To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions