Histone methyltransferase activity affects metabolism in human cells independently of transcriptional regulation.

The N-terminal tails of eukaryotic histones are frequently posttranslationally modified. The role of these modifications in transcriptional regulation is well-documented. However, the extent to which the enzymatic processes of histone posttranslational modification might affect metabolic regulation is less clear. Here, we investigated how histone methylation might affect metabolism using metabolomics, proteomics, and RNA-seq data from cancer cell lines, primary tumour samples and healthy tissue samples. In cancer, the expression of histone methyltransferases (HMTs) was inversely correlated to the activity of NNMT, an enzyme previously characterised as a methyl sink that disposes of excess methyl groups carried by the universal methyl donor S-adenosyl methionine (SAM or AdoMet). In healthy tissues, histone methylation was inversely correlated to the levels of an alternative methyl sink, PEMT. These associations affected the levels of multiple histone marks on chromatin genome-wide but had no detectable impact on transcriptional regulation. We show that HMTs with a variety of different associations to transcription are co-regulated by the Retinoblastoma (Rb) tumour suppressor in human cells. Rb-mutant cancers show increased total HMT activity and down-regulation of NNMT. Together, our results suggest that the total activity of HMTs affects SAM metabolism, independent of transcriptional regulation.

Fluctuations in chromatin state at regulatory loci occur spontaneously under relaxed selection and are associated with epigenetically inherited variation in C. elegans gene expression.

Some epigenetic information can be transmitted between generations without changes in the underlying DNA sequence. Changes in epigenetic regulators, termed epimutations, can occur spontaneously and be propagated in populations in a manner reminiscent of DNA mutations. Small RNA-based epimutations occur in C. elegans and persist for around 3-5 generations on average. Here, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational inheritance of gene expression changes. We compared the chromatin and gene expression profiles at matched time points from three independent lineages of C. elegans propagated at minimal population size. Spontaneous changes in chromatin occurred in around 1% of regulatory regions each generation. Some were heritable epimutations and were significantly enriched for heritable changes in expression of nearby protein-coding genes. Most chromatin-based epimutations were short-lived but a subset had longer duration. Genes subject to long-lived epimutations were enriched for multiple components of xenobiotic response pathways. This points to a possible role for epimutations in adaptation to environmental stressors.

Ether lipid deficiency disrupts lipid homeostasis leading to ferroptosis sensitivity.

Ferroptosis is an iron-dependent form of regulated cell death associated with uncontrolled membrane lipid peroxidation and destruction. Previously, we showed that dietary dihomo-gamma-linolenic acid (DGLA; 20: 3(n-6)) triggers ferroptosis in the germ cells of the model organism, Caenorhabditis elegans. We also demonstrated that ether lipid-deficient mutant strains are sensitive to DGLA-induced ferroptosis, suggesting a protective role for ether lipids. The vinyl ether bond unique to plasmalogen lipids has been hypothesized to function as an antioxidant, but this has not been tested in animal models. In this study, we used C. elegans mutants to test the hypothesis that the vinyl ether bond in plasmalogens acts as an antioxidant to protect against germ cell ferroptosis as well as to protect from whole-body tert-butyl hydroperoxide (TBHP)-induced oxidative stress. We found no role for plasmalogens in either process. Instead, we demonstrate that ether lipid-deficiency disrupts lipid homeostasis in C. elegans, leading to altered ratios of saturated and monounsaturated fatty acid (MUFA) content in cellular membranes. We demonstrate that ferroptosis sensitivity in both wild type and ether-lipid deficient mutants can be rescued in several ways that change the relative abundance of saturated fats, MUFAs and specific polyunsaturated fatty acids (PUFAs). Specifically, we reduced ferroptosis sensitivity by (1) using mutant strains unable to synthesize DGLA, (2) using a strain carrying a gain-of-function mutation in the transcriptional mediator MDT-15, or (3) by dietary supplementation of MUFAs. Furthermore, our studies reveal important differences in how dietary lipids influence germ cell ferroptosis versus whole-body peroxide-induced oxidative stress. These studies highlight a potentially beneficial role for endogenous and dietary MUFAs in the prevention of ferroptosis.

Dynamics of asymmetric membranes and interleaflet coupling as intermediates in membrane fusion.

Membrane fusion is a tool to increase the complexity of model membrane systems. Here, we use silica nanoparticles to fuse liquid-disordered DOPC giant unilamellar vesicles (GUVs) and liquid-ordered DPPC:cholesterol (7:3) GUVs. After fusion, GUVs display large membrane domains as confirmed by fluorescence confocal microscopy. Laurdan spectral imaging of the membrane phases in the fused GUVs shows differences compared with the initial vesicles indicating some lipid redistribution between phase domains as dictated by the tie lines of the phase diagram. Remarkably, using real-time confocal microscopy we were able to record the dynamics of formation of asymmetric membrane domains in hemifused GUVs and detected interleaflet coupling phenomena by which the DOPC-rich liquid-disordered domains in outer monolayer modulates the phase state of the DPPC:cholesterol inner membrane leaflet which transitions from liquid-ordered to liquid-disordered phase. We find that internal membrane stresses generated by membrane asymmetry enhance the efficiency of full fusion compared with our previous studies on symmetric vesicle fusion. Furthermore, under these conditions, the liquid-disordered monolayer dictates the bilayer phase state of asymmetric membrane domains in >90% of observed cases. By comparison to the findings of previous literature, we suggest that the monolayer phase that dominates the bilayer properties could be a mechanoresponsive signaling mechanism sensitive to the local membrane environment.

Branched actin cortices reconstituted in vesicles sense membrane curvature.

The actin cortex is a complex cytoskeletal machinery that drives and responds to changes in cell shape. It must generate or adapt to plasma membrane curvature to facilitate diverse functions such as cell division, migration, and phagocytosis. Due to the complex molecular makeup of the actin cortex, it remains unclear whether actin networks are inherently able to sense and generate membrane curvature, or whether they rely on their diverse binding partners to accomplish this. Here, we show that curvature sensing is an inherent capability of branched actin networks nucleated by Arp2/3 and VCA. We develop a robust method to encapsulate actin inside giant unilamellar vesicles (GUVs) and assemble an actin cortex at the inner surface of the GUV membrane. We show that actin forms a uniform and thin cortical layer when present at high concentration and distinct patches associated with negative membrane curvature at low concentration. Serendipitously, we find that the GUV production method also produces dumbbell-shaped GUVs, which we explain using mathematical modeling in terms of membrane hemifusion of nested GUVs. We find that branched actin networks preferentially assemble at the neck of the dumbbells, which possess a micrometer-range convex curvature comparable with the curvature of the actin patches found in spherical GUVs. Minimal branched actin networks can thus sense membrane curvature, which may help mammalian cells to robustly recruit actin to curved membranes to facilitate diverse cellular functions such as cytokinesis and migration.

Genome analysis of haloalkaline isolates from the soda saline crater lake of Isabel Island; comparative genomics and potential metabolic analysis within the genus Halomonas.

BACKGROUND: Isabel Island is a Mexican volcanic island primarily composed of basaltic stones. It features a maar known as Laguna Fragatas, which is classified as a meromictic thalassohaline lake. The constant deposition of guano in this maar results in increased levels of phosphorus, nitrogen, and carbon. The aim of this study was to utilize high-quality genomes from the genus Halomonas found in specialized databases as a reference for genome mining of moderately halophilic bacteria isolated from Laguna Fragatas. This research involved genomic comparisons employing phylogenetic, pangenomic, and metabolic-inference approaches. RESULTS: The Halomonas genus exhibited a large open pangenome, but several genes associated with salt metabolism and homeostatic regulation (ectABC and betABC), nitrogen intake through nitrate and nitrite transporters (nasA, and narGI), and phosphorus uptake (pstABCS) were shared among the Halomonas isolates. CONCLUSIONS: The isolated bacteria demonstrate consistent adaptation to high salt concentrations, and their nitrogen and phosphorus uptake mechanisms are highly optimized. This optimization is expected in an extremophile environment characterized by minimal disturbances or abrupt seasonal variations. The primary significance of this study lies in the dearth of genomic information available for this saline and low-disturbance environment. This makes it important for ecosystem conservation and enabling an exploration of its biotechnological potential. Additionally, the study presents the first two draft genomes of H. janggokensis.

A compendium of kinetic modulatory profiles identifies ferroptosis regulators.

Cell death can be executed by regulated apoptotic and nonapoptotic pathways, including the iron-dependent process of ferroptosis. Small molecules are essential tools for studying the regulation of cell death. Using time-lapse imaging and a library of 1,833 bioactive compounds, we assembled a large compendium of kinetic cell death modulatory profiles for inducers of apoptosis and ferroptosis. From this dataset we identify dozens of ferroptosis suppressors, including numerous compounds that appear to act via cryptic off-target antioxidant or iron chelating activities. We show that the FDA-approved drug bazedoxifene acts as a potent radical trapping antioxidant inhibitor of ferroptosis both in vitro and in vivo. ATP-competitive mechanistic target of rapamycin (mTOR) inhibitors, by contrast, are on-target ferroptosis inhibitors. Further investigation revealed both mTOR-dependent and mTOR-independent mechanisms that link amino acid metabolism to ferroptosis sensitivity. These results highlight kinetic modulatory profiling as a useful tool to investigate cell death regulation.

Maternal age generates phenotypic variation in Caenorhabditis elegans.

Genetically identical individuals that grow in the same environment often show substantial phenotypic variation within populations of organisms as diverse as bacteria, nematodes, rodents and humans. With some exceptions, the causes are poorly understood. Here we show that isogenic Caenorhabditis elegans nematodes vary in their size at hatching, speed of development, growth rate, starvation resistance, fecundity, and also in the rate of development of their germline relative to that of somatic tissues. We show that the primary cause of this variation is the age of an individual's mother, with the progeny of young mothers exhibiting several phenotypic impairments. We identify age-dependent changes in the maternal provisioning of the lipoprotein complex vitellogenin to embryos as the molecular mechanism that underlies the variation in multiple traits throughout the life of an animal. The production of sub-optimal progeny by young mothers may reflect a trade-off between the competing fitness traits of a short generation time and the survival and fecundity of the progeny.

Improvement of Akanthomyces lecanii resistance to tebuconazole through UV-C radiation and selective pressure on microbial evolution and growth arenas.

Tebuconazole (TEB) is a fungicide widely used in agriculture; however, its constant application has increased the emergence of resistant plant pathogenic fungal strains and reduced the effectiveness of fungi as biological control agents; for instance, the entomopathogenic and hyperparasitic fungus Akanthomyces lecanii, suitable for simultaneous biological control of insect pest and plant pathogenic fungi, is highly sensitive to fungicides. We carried out the induction of resistance to TEB in two wild type strains of A. lecanii by UV radiation and selective pressure in increasing fungicide gradients using a modified Microbial Evolution and Growth Arena (MEGA), to produce A. lecanii strains that can be used as biological control agent in the presence of tebuconazole. Nine UV-induced and three naturally adapted A. lecanii strains were resistant to TEB at the agriculturally recommended dose, and three irradiated strains were resistant to TEB concentration ten times higher; moreover, growth, sporulation rates, production of hydrolytic enzymes, and virulence against the hemipteran Coccus viridis, a major pest of coffee crops, were not affected in the TEB-resistant strains. These A. lecanii TEB-resistant strains would have a greater opportunity to develop and to establish themselves in fields where the fungicide is present and can be used in a combined biological-chemical strategy to improve insect and plant pathogenic fungal control in agriculture. Also, the selective pressure through modified MEGA plate methodology can be used for the adaptation of entomopathogenic filamentous fungi to withstand other chemical or abiotic stresses that limits its effectiveness for pest control.

The U-wave: A remaining enigma of the electrocardiogram.

The U-wave's electrophysiological origin remains unknown and is subject to debate. It is rarely used for diagnosis in clinical practice. The aim of this study was to review new information regarding the U-wave. Further to present the proposed theories behind the U-wave's origin along with potential pathophysiologic and prognostic implications related to its presence, polarity and morphology. METHOD: Literature searches were conducted to retrieve publications related to the electrocardiogram U-wave in the literature database Embase. RESULTS: The review of the literature revealed the following major theories that will be discussed; late depolarisation, delayed or prolonged repolarisation, electro-mechanical stretch and IK1 dependent intrinsic potential differences in the terminal part of the action potential. Various pathologic conditions were found to correlate with the presence and properties of the U-wave, such as its amplitude and polarity. Abnormal U-waves can, for example, be observed in coronary artery disease with ongoing myocardial ischemia or infarction, ventricular hypertrophy, congenital heart disease, primary cardiomyopathy and valvular defects. Negative U-waves are highly specific for the presence of heart diseases. Concordantly negative T- and U-waves are especially associated with cardiac disease. Patients with negative U-waves tend to have higher blood pressure and history of hypertension, higher heart rate, cardiac disease and left ventricular hypertrophy compared to subjects with normal U-waves. Negative U-waves have been found to be associated with increased risk of all-cause mortality, cardiac death and cardiac hospitalisation in men. CONCLUSIONS: The origin of the U-wave is still not established. U-wave diagnostics may reveal cardiac disorders and the cardiovascular prognosis. Including the U-wave characteristics in the clinical ECG assessment may be useful.

An immersive virtual reality system for ecological assessment of peripersonal and extrapersonal unilateral spatial neglect.

BACKGROUND: Unilateral spatial neglect (USN) is a debilitating neuropsychological syndrome that often follows brain injury, in particular a stroke affecting the right hemisphere. In current clinical practice, the assessment of neglect is based on old-fashioned paper-and-pencil and behavioral tasks, and sometimes relies on the examiner's subjective judgment. Therefore, there is a need for more exhaustive, objective and ecological assessments of USN. METHODS: In this paper, we present two tasks in immersive virtual reality to assess peripersonal and extrapersonal USN. The tasks are designed with several levels of difficulty to increase sensitivity of the assessment. We then validate the feasibility of both assessments in a group of healthy adult participants. RESULTS: We report data from a study with a group of neurologically unimpaired participants (N = 39). The results yield positive feedback on comfort, usability and design of the tasks. We propose new objective scores based on participant's performance captured by head gaze and hand position information, including, for instance, time of exploration, moving time towards left/right and time-to-reach, which could be used for the evaluation of the attentional spatial bias with neurological patients. Together with the number of omissions, the new proposed parameters can result in lateralized index ratios as a measure of asymmetry in space exploration. CONCLUSIONS: We presented two innovative assessments for USN based on immersive virtual reality, evaluating the far and the near space, using ecological tasks in multimodal, realistic environments. The proposed protocols and objective scores can help distinguish neurological patients with and without USN.

Protein corona alters the mechanisms of interaction between silica nanoparticles and lipid vesicles.

The use of nanoparticles (NPs) for biomedical applications implies their delivery into the organism where they encounter biological fluids. In such biological fluids, proteins and other biomolecules adhere to the surface of the NPs forming a biomolecular corona that can alter significantly the behaviour of the nanomaterials. Here, we investigate the impact of a bovine serum albumin corona on interactions between silica nanoparticles (SNPs) of two different sizes and giant lipid vesicles. The formation of the protein corona leads to a significant increase of the hydrodynamic size of the SNPs. Confocal microscopy imaging shows that the protein corona alters the morphological response of vesicles to SNPs. In addition, Laurdan spectral imaging show that the protein corona weakens the effect of SNPs on the lipid packing in the GUV membrane. Our results demonstrate that a protein corona can change the interaction mechanism between nanoparticles and lipid membranes.

Socio-economic impact of Covid-19 on the fishing sector: A case study of a region highly dependent on fishing in Spain.

Galicia is the most important fishing region in Spain. Nearly 50% of the volume of catches and of the national fishing fleet are concentrated in this region. During the Covid-19 pandemic, the fishing sector had the status of an essential sector and was not forced to stop its activity by the national Government. However, its economic performance has deteriorated in 2020. This article aims to analyze the impact of the pandemic on the extractive fishing sector in Galicia. For this purpose, the performance of the main economic and financial variables of the 246 companies that constitute this industry has been studied. The companies pertain to different extractive sectors (the national, offshore and large-scale fleets) and are in 9 different areas (Vigo, Pontevedra, Arousa, Muros, Fisterra, Costa da Morte, A Coruña-Ferrol, Cedeira and A Mariña). The results of the analysis show that the 9 fishing zones share a generalized negative trend but that there is heterogeneity in the results. Among the most determining factors are the predominant fleet extract, the target species caught, or the perception of public subsidies.

microRNA expression variation as a potential molecular mechanism contributing to adaptation to hydrogen sulphide.

microRNAs (miRNAs) are post-transcriptional regulators of gene expression and can play an important role in modulating organismal development and physiology in response to environmental stress. However, the role of miRNAs in mediating adaptation to diverse environments in natural study systems remains largely unexplored. Here, we characterized miRNAs and their expression in Poecilia mexicana, a species of small fish that inhabits both normal streams and extreme environments in the form of springs rich in toxic hydrogen sulphide (H2 S). We found that P. mexicana has a similar number of miRNA genes as other teleosts. In addition, we identified a large population of mature miRNAs that were differentially expressed between locally adapted populations in contrasting habitats, indicating that miRNAs may contribute to P. mexicana adaptation to sulphidic environments. In silico identification of differentially expressed miRNA-mRNA pairs revealed, in the sulphidic environment, the downregulation of miRNAs predicted to target mRNAs involved in sulphide detoxification and cellular homeostasis, which are pathways essential for life in H2 S-rich springs. In addition, we found that predicted targets of upregulated miRNAs act in the mitochondria (16.6% of predicted annotated targets), which is the main site of H2 S toxicity and detoxification, possibly modulating mitochondrial function. Together, the differential regulation of miRNAs between these natural populations suggests that miRNAs may be involved in H2 S adaptation by promoting functions needed for survival and reducing functions affected by H2 S. This study lays the groundwork for further research to directly demonstrate the role of miRNAs in adaptation to H2 S. Overall, this study provides a critical stepping-stone towards a comprehensive understanding of the regulatory mechanisms underlying the adaptive variation in gene expression in a natural system.

Biomimetic Curvature and Tension-Driven Membrane Fusion Induced by Silica Nanoparticles.

Fusion events in living cells are intricate phenomena that require the coordinate action of multicomponent protein complexes. However, simpler synthetic tools to control membrane fusion in artificial cells are highly desirable. Native membrane fusion machinery mediates fusion, driving a delicate balance of membrane curvature and tension between two closely apposed membranes. Here, we show that silica nanoparticles (SiO2 NPs) at a size close to the cross-over between tension-driven and curvature-driven interaction regimes initiate efficient fusion of biomimetic model membranes. Fusion efficiency and mechanisms are studied by Förster resonance energy transfer and confocal fluorescence microscopy. SiO2 NPs induce a slight increase in lipid packing likely to increase the lateral tension of the membrane. We observe a connection between membrane tension and fusion efficiency. Finally, real-time confocal fluorescence microscopy reveals three distinct mechanistic pathways for membrane fusion. SiO2 NPs show significant potential for inclusion in the synthetic biology toolkit for membrane remodeling and fusion in artificial cells.

Rationale and protocol of the StayFitLonger study: a multicentre trial to measure efficacy and adherence of a home-based computerised multidomain intervention in healthy older adults.

BACKGROUND: In older adults, multidomain training that includes physical and cognitive activities has been associated with improvement of physical and cognitive health. The goal of the multisite StayFitLonger study is to assess a home-based computerised training programme, which combines physical exercises, stimulating cognitive activities and virtual coaching. METHODS: One hundred twenty-eight cognitively healthy older adults will be recruited from the community in Switzerland, Canada and Belgium. The study will comprise (1) a 26-week double-blind randomized controlled efficacy trial and (2) a 22-week pragmatic adherence sub-study. In the efficacy trial, participants will be randomly assigned to an experimental or an active control intervention. In the experimental intervention, participants will use the StayFitLonger programme, which is computerised on a tablet and provides content that combines physical activities with a focus on strength and balance, as well as divided attention, problem solving and memory training. Outcomes will be measured before and after 26 weeks of training. The primary efficacy outcome will be performance on the "Timed-Up & Go" test. Secondary outcomes will include measures of frailty, cognition, mood, fear of falling, quality of life, and activities of daily living. Age, sex, education, baseline cognition, expectation, and adherence will be used as moderators of efficacy. Following the 26-week efficacy trial, all participants will use the experimental programme meaning that participants in the control group will 'cross over' to receive the StayFitLonger programme for 22 weeks. Adherence will be measured in both groups based on dose, volume and frequency of use. In addition, participants' perception of the programme and its functionalities will be characterised through usability, acceptability and user experience. DISCUSSION: This study will determine the efficacy, adherence and participants' perception of a home-based multidomain intervention programme and its functionalities. This will allow for further development and possible commercialization of a scientifically validated training programme. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04237519 Registered on January 22, 2020 - Retrospectively registered.

Mechanomodulation of Lipid Membranes by Weakly Aggregating Silver Nanoparticles.

Silver nanoparticles (AgNPs) have wide-ranging applications, including as additives in consumer products and in medical diagnostics and therapy. Therefore, understanding how AgNPs interact with biological systems is important for ascertaining any potential health risks due to the likelihood of high levels of human exposure. Besides any severe, acute effects, it is desirable to understand more subtle interactions that could lead to milder, chronic health impacts. Nanoparticles are small enough to be able to enter biological cells and interfere with their internal biochemistry. The initial contact between the nanoparticle and cell is at the plasma membrane. To gain fundamental mechanistic insight into AgNP-membrane interactions, we investigate these phenomena in minimal model systems using a wide range of biophysical approaches applied to lipid vesicles. We find a strong dependence on the medium composition, where colloidally stable AgNPs in a glucose buffer have a negligible effect on the membrane. However, at physiological salt concentrations, the AgNPs start to weakly aggregate and sporadic but significant membrane perturbation events are observed. Under these latter conditions, transient poration and structural remodeling of some vesicle membranes are observed. We observe that the fluidity of giant vesicle membranes universally decreases by an average of 16% across all vesicles. However, we observe a small population of vesicles that display a significant change in their mechanical properties with lower bending rigidity and higher membrane tension. Therefore, we argue that the isolated occurrences of membrane perturbation by AgNPs are due to low-probability mechanomodulation by AgNP aggregation at the membrane.

Solid-state fermentation of Bacillus thuringiensis var kurstaki HD-73 maintains higher biomass and spore yields as compared to submerged fermentation using the same media.

To determine the growth kinetic parameters, substrate consumption and spore yields for Bacillus thuringiensis, liquid fermentation (SmF) and solid-state fermentation (SSF), on polyurethane foam (PUF), were analysed comprising strictly the same media. The analysis included three medium concentrations, maintaining the same C/N ratio, with initial glucose at 12.5, 25, and 50 g L-1 (1X, 2X and 4X, respectively). SSF at 2X and 4X produced higher amounts of total biomass, vegetative growth and even early sporulation. Notably, at all glucose concentrations, sporulation was not inhibited in SSF as seen partially in SmF at 2X, and totally at 4X. Micrographs from PUF cultures showed thin layers of bacteria forming large horizontal aggregates, associated with the higher biomass yields and the early cell differentiation. This is the first work showing that SSF improves spore yields of B. thuringiensis in media with high substrate concentrations, using PUF as a research tool for comparative analysis with application in new production systems including biofilm-forming microorganisms.

A Miniaturized Multiband Antenna Array for Robust Navigation in Aerial Applications.

Satellite navigation is more and more important in a plethora of very different application fields, ranging from bank transactions to shipping, from autonomous driving to aerial applications, such as avionics as well as unmanned aerial vehicles (UAVs). Due to the increasing dependency on satellite navigation, the need for robust systems able to counteract unintentional or intentional interferences is growing. When considering interference-robust designs; however, the complexity increases. Top performance is obtained through the use of multi-antenna receivers capable of performing spatial nulling in the direction of the interference signals. In particular, mobile applications (aeronautics, UAVs, automotive) have a substantial interest in robust navigation, but they also have the strongest constraints on the weight and available places for installation, with the use of bigger and heavier systems posing a substantial problem. In order to overcome this limitation, the present work shows a miniaturized five element (4+1) antenna array, which operates at the L1/E1 band (with array capability), as well as at the L5/E5 band (as a single antenna). The proposed antenna array is able to fit into a 3.5-inch footprint, i.e., is compliant with the most widespread footprints for single antennas. Moreover, it is capable of multiband operation and meets the requirements of dual-frequency multi-constellation (DFMC) systems. Thanks to its extreme miniaturization and its compliance with current airborne single antenna footprints, the presented antenna array is suitable for easy integration in future aerial platforms, while enabling robustness and enhancing interference mitigation techniques using multi-antenna processing.

Virtual reality experiences, embodiment, videogames and their dimensions in neurorehabilitation.

BACKGROUND: In the context of stroke rehabilitation, new training approaches mediated by virtual reality and videogames are usually discussed and evaluated together in reviews and meta-analyses. This represents a serious confounding factor that is leading to misleading, inconclusive outcomes in the interest of validating these new solutions. MAIN BODY: Extending existing definitions of virtual reality, in this paper I put forward the concept of virtual reality experience (VRE), generated by virtual reality systems (VRS; i.e. a group of variable technologies employed to create a VRE). Then, I review the main components composing a VRE, and how they may purposely affect the mind and body of participants in the context of neurorehabilitation. In turn, VRS are not anymore exclusive from VREs but are currently used in videogames and other human-computer interaction applications in different domains. Often, these other applications receive the name of virtual reality applications as they use VRS. However, they do not necessarily create a VRE. I put emphasis on exposing fundamental similarities and differences between VREs and videogames for neurorehabilitation. I also recommend describing and evaluating the specific features encompassing the intervention rather than evaluating virtual reality or videogames as a whole. CONCLUSION: This disambiguation between VREs, VRS and videogames should help reduce confusion in the field. This is important for databases searches when looking for specific studies or building metareviews that aim at evaluating the efficacy of technology-mediated interventions.