The microbiome-gut-brain axis in acute and chronic brain diseases

The gut microbiome — the largest reservoir of microorganisms of the human body — is emerging as an important player in neurodevelopment and ageing as well as in brain diseases including stroke, Alzheimer’s disease and Parkinson’s disease. The growing knowledge on mediators and triggered pathways has advanced our understanding of the interactions along the gut-brain axis. Gut bacteria produce neuroactive compounds and can modulate neuronal function, plasticity and behavior. Furthermore, intestinal microorganisms impact the host’s metabolism and immune status which in turn affect neuronal pathways in the enteric and central nervous systems. Here, we discuss the recent insights from human studies and animal models on the bi-directional communication along the microbiome-gut-brain axis in both acute and chronic brain diseases

A Semi-Quantitative, Synteny-Based Method to Improve Functional Predictions for Hypothetical and Poorly Annotated Bacterial and Archaeal Genes

During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial genomes from the NCBI database and four newly assembled genomes of uncultivated Archaea from an acid mine drainage (AMD) community. In parallel, we established and modeled the trend between synteny and functional relatedness in the 118 genomes available in the STRING database. By combining these models, we developed a gene functional annotation method that weights evolutionary distance to estimate the probability of functional associations of syntenous proteins between genome pairs. The method was applied to the hypothetical proteins and poorly annotated genes in newly assembled acid mine drainage Archaeal genomes to add or improve gene annotations. This is the first method to assign possible functions to poorly annotated genes through quantification of the probability of gene functional relationships based on synteny at a significant evolutionary distance, and has the potential for broad application

Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq

The utilisation of genome-wide transcriptomics has played a pivotal role in advancing the field of toxicology, allowing the mapping of transcriptional signatures to chemical exposures. These activities have uncovered several transcriptionally regulated pathways that can be utilised for assessing the perturbation impact of a chemical and also the identification of toxic mode of action. However, current transcriptomic platforms are not very amenable to high-throughput workflows due to, high cost, complexities in sample preparation and relatively complex bioinformatic analysis. Thus, transcriptomic investigations are usually limited in dose and time dimensions and are, therefore, not optimal for implementation in risk assessment workflows. In this study, we investigated a new cost-effective, transcriptomic assay, TempO-Seq, which alleviates the aforementioned limitations. This technique was evaluated in a 6-compound screen, utilising differentiated kidney (RPTEC/TERT1) and liver (HepaRG) cells and compared to non-transcriptomic label-free sensitive endpoints of chemical-induced disturbances, namely phase contrast morphology, xCELLigence and glycolysis. Non-proliferating cell monolayers were exposed to six sub-lethal concentrations of each compound for 24 h. The results show that utilising a 2839 gene panel, it is possible to discriminate basal tissue-specific signatures, generate dose-response relationships and to discriminate compound-specific and cell type-specific responses. This study also reiterates previous findings that chemical-induced transcriptomic alterations occur prior to cytotoxicity and that transcriptomics provides in depth mechanistic information of the effects of chemicals on cellular transcriptional responses. TempO-Seq is a robust transcriptomic platform that is well suited for in vitro toxicity experiments.Horizon 2020(H2020)68100

Inertial Sensor-Based Motion Tracking in Football with Movement Intensity Quantification

Inertial sensor-based measurements of lower body kinematics in football players may improve physical load estimates during training sessions and matches. However, the validity of inertial-based motion analysis systems is specific to both the type of movement and the intensity at which movements are executed. Importantly, such a system should be relatively simple, so it can easily be used in daily practice. This paper introduces an easy-to-use inertial-based motion analysis system and evaluates its validity using an optoelectronic motion analysis system as a gold standard. The system was validated in 11 football players for six different football specific movements that were executed at low, medium, and maximal intensity. Across all movements and intensities, the root mean square differences (means ± SD) for knee and hip flexion/extension angles were 5.3° ± 3.4° and 8.0° ± 3.5°, respectively, illustrating good validity with the gold standard. In addition, mean absolute flexion/extension angular velocities significantly differed between the three movement intensities. These results show the potential to use the inertial based motion analysis system in football practice to obtain lower body kinematics and to quantify movement intensity, which both may improve currently used physical load estimates of the players

Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments

Biological and Soft Matter Physic