Toward Predicting Motion Sickness Using Virtual Reality and a Moving Platform Assessing Brain, Muscles, and Heart Signals

Motion sickness (MS) and postural control (PC) conditions are common complaints among those who passively travel. Many theories explaining a probable cause for MS have been proposed but the most prominent is the sensory conflict theory, stating that a mismatch between vestibular and visual signals causes MS. Few measurements have been made to understand and quantify the interplay between muscle activation, brain activity, and heart behavior during this condition. We introduce here a novel multimetric system called BioVRSea based on virtual reality (VR), a mechanical platform and several biomedical sensors to study the physiology associated with MS and seasickness. This study reports the results from 28 individuals: the subjects stand on the platform wearing VR goggles, a 64-channel EEG dry-electrode cap, two EMG sensors on the gastrocnemius muscles, and a sensor on the chest that captures the heart rate (HR). The virtual environment shows a boat surrounded by waves whose frequency and amplitude are synchronized with the platform movement. Three measurement protocols are performed by each subject, after each of which they answer the Motion Sickness Susceptibility Questionnaire. Nineteen parameters are extracted from the biomedical sensors (5 from EEG, 12 from EMG and, 2 from HR) and 13 from the questionnaire. Eight binary indexes are computed to quantify the symptoms combining all of them in the Motion Sickness Index (IMS). These parameters create the MS database composed of 83 measurements. All indexes undergo univariate statistical analysis, with EMG parameters being most significant, in contrast to EEG parameters. Machine learning (ML) gives good results in the classification of the binary indexes, finding random forest to be the best algorithm (accuracy of 74.7 for IMS). The feature importance analysis showed that muscle parameters are the most relevant, and for EEG analysis, beta wave results were the most important. The present work serves as the first step in identifying the key physiological factors that differentiate those who suffer from MS from those who do not using the novel BioVRSea system. Coupled with ML, BioVRSea is of value in the evaluation of PC disruptions, which are among the most disturbing and costly health conditions affecting humans

Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma

Giant congenital naevi are pigmented childhood lesions that frequently lead to melanoma, the most aggressive skin cancer. The mechanisms underlying this malignancy are largely unknown, and there are no effective therapies. Here we describe a mouse model for giant congenital naevi and show that naevi and melanoma prominently express Sox10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox10 haploinsufficiency counteracts Nras(Q61K)-driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox10 is also crucial for the maintenance of neoplastic cells in vivo. In human patients, virtually all congenital naevi and melanomas are SOX10 positive. Furthermore, SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and completely abolishes in vivo tumour formation. Thus, SOX10 represents a promising target for the treatment of congenital naevi and melanoma in human patients

Functional Murine Leukemia Virus Vectors Pseudotyped with the Visna Virus Envelope Show Expanded Visna Virus Cell Tropism

Pseudotype virus vectors serve as a powerful tool for the study of virus receptor usage and entry. We describe the development of murine leukemia virus (MuLV) particles pseudotyped with the visna virus envelope glycoprotein and encoding a green fluorescent protein reporter as a tool to study the expression of the visna virus receptor. Functional MuLV/visna virus pseudotypes were obtained when the cytoplasmic tail of the visna virus envelope TM protein was truncated to 3, 7, or 11 amino acids in length. MuLV/visna virus particles were used to transduce a panel of cell types from various organisms, including sheep, goat, human, hamster, mouse, monkey, and quail. The majority of the cells examined were susceptible to MuLV/visna pseudotype viruses, supporting the notion that the visna virus cellular receptor is a widely expressed protein found in many species. Of 16 different cell types tested, only mouse embryo fibroblast NIH 3T3 cells, hamster ovary CHO cells, and the human promonocyte cell line U937 cells were not susceptible to transduction by the pseudotyped virus. The production of functional MuLV/visna virus pseudotypes has provided a sensitive, biologically relevant system to study visna virus cell entry and envelope-receptor interactions

WNT5A-Mediated β-Catenin-Independent Signalling is a Novel Regulator of Cancer Cell Metabolism

WNT5A has been identified as an important ligand in the malignant progression of a number of tumours. Although WNT5A signalling is often altered in cancer, the ligand(')s role as either a tumour suppressor or oncogene varies between tumour types and is a contemporary issue for investigators of β-catenin (CTNNB1)-independent WNT signalling in oncology. Here we report that one of the initial effects of active WNT5A signalling in malignant melanoma cells is an alteration in cellular energy metabolism and specifically an increase in aerobic glycolysis. This was found to be at least in part due to an increase in active Akt signalling and lactate dehydrogenase (LDH) activity. The clinical relevance of these findings was strengthened by a strong correlation (

Sox10 Controls Migration of B16F10 Melanoma Cells through Multiple Regulatory Target Genes

It is believed that the inherent differentiation program of melanocytes during embryogenesis predisposes melanoma cells to high frequency of metastasis. Sox10, a transcription factor expressed in neural crest stem cells and a subset of progeny lineages, plays a key role in the development of melanocytes. We show that B16F10 melanoma cells transfected with siRNAs specific for Sox10 display reduced migratory activity which in turn indicated that a subset of transcriptional regulatory target genes of Sox10 is likely to be involved in migration and metastasis of melanoma cells. We carried out a microarray-based gene expression profiling using a Sox10-specific siRNA to identify relevant regulatory targets and found that multiple genes including melanocortin-1 receptor (Mc1r) partake in the regulation of migration. We provide evidences that the effect of Sox10 on migration is mediated in large part by Mitf, a transcription factor downstream to Sox10. Among the mouse melanoma cell lines examined, however, only B16F10 showed robust down-regulation of Sox10 and inhibition of cell migration indicating that further dissection of dosage effects and/or cell line-specific regulatory networks is necessary. The involvement of Mc1r in migration was studied in detail in vivo using a murine metastasis model. Specifically, B16F10 melanoma cells treated with a specific siRNA showed reduced tendency in metastasizing to and colonizing the lung after being injected in the tail vein. These data reveal a cadre of novel regulators and mediators involved in migration and metastasis of melanoma cells that represents potential targets of therapeutic intervention