Ceramide, cholesterol, and phosphatidic acid are major basic structures for cell membrane lipids. These lipids are modified with glucose to generate glucosylceramide (GlcCer), cholesterylglucoside (ChlGlc), and phosphatidylglucoside (PtdGlc), respectively. Glucosylation dramatically changes the functional properties of lipids. For instance, ceramide acts as a strong tumor suppressor that causes apoptosis and cell cycle arrest, while GlcCer has an opposite effect, downregulating ceramide activities. All glucosylated lipids are enriched in lipid rafts or microdomains and play fundamental roles in a variety of cellular processes. In this review, we discuss the biological functions and metabolism of these three glucosylated lipids.
The Drosophila retinal degeneration A (rdgA) mutant has photoreceptor cells that degenerate within a week after eclosion. The degeneration starts with the disruption of the subrhabdomeric cisternae (SRC), which are the organelles essential for the transport of phospholipids to the photoreceptive membranes. Our previous biochemical and molecular studies suggested that the rdgA gene encodes an eye-specific diacylglycerol kinase (DGK). In this study, we show that retinal degeneration is prevented by the introduction of the eye-DGK gene in the rdgA mutant genome, suggesting that the DGK activity is crucial for the maintenance of the photoreceptor. Furthermore, by immunohistochemical analysis, we have demonstrated that the rdgA protein is predominantly associated with the SRC, suggesting that the conversion from diacylglycerol (DG) to phosphatidic acid (PA) most actively occurs in SRC. The analysis of the eyes of mutants homozygous for rdgA and eye-protein kinase C mutations indicates that retinal degeneration is caused by the deficiency of PA rather than excessive accumulation of DG. From these data, we conclude that the production of PA in the SRC membranes is essential for the maintenance of the photoreceptor.
Background: This study aimed to propose an experiential approach for understanding color vision variation using virtual reality technology.Methods: The study design was adapted from the phase 1 clinical trial for medical apps. A virtual classroom was developed in a three-dimensional space, and ten healthy university students were tested to understand color vision variations.Results: No participant interrupted the experience due to VR sickness. Most participants noted that the virtual classroom was an excellent educational tool, which could help teachers understand the problems associated with [visual analog scale (VAS): mean ± standard deviation (SD), 9.6 ± 0.6] and obtain a better understanding of (VAS: mean ± SD, 9.0 ± 1.0) color vision deficiencies.Conclusions: A pilot study was conducted on the impact of immersive virtual classroom experiences as an educational tool for color barrier-free presentations. This approach may help the participants to respond appropriately to children who suffer from this disorder. It is necessary to evaluate the impact of this approach on new teachers.
Alpha-synuclein (αSyn) plays a central role in the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Recent multicenter genetic studies have revealed that mutations in the glucocerebrosidase 1 (GBA1) gene, which are responsible for Gaucher's disease, are strong risk factors for PD and DLB. However, the mechanistic link between the functional loss of glucocerebrosidase (GCase) and the toxicity of αSyn in vivo is not fully understood. In this study, we employed Drosophila models to examine the effect of GCase deficiency on the neurotoxicity of αSyn and its molecular mechanism. Behavioral and histological analyses showed that knockdown of the Drosophila homolog of GBA1 (dGBA1) exacerbates the locomotor dysfunction, loss of dopaminergic neurons and retinal degeneration of αSyn-expressing flies. This phenotypic aggravation was associated with the accumulation of proteinase K (PK)-resistant αSyn, rather than with changes in the total amount of αSyn, raising the possibility that glucosylceramide (GlcCer), a substrate of GCase, accelerates the misfolding of αSyn. Indeed, in vitro experiments revealed that GlcCer directly promotes the conversion of recombinant αSyn into the PK-resistant form, representing a toxic conformational change. Similar to dGBA1 knockdown, knockdown of the Drosophila homolog of β-galactosidase (β-Gal) also aggravated locomotor dysfunction of the αSyn flies, and its substrate GM1 ganglioside accelerated the formation of PK-resistant αSyn. Our findings suggest that the functional loss of GCase or β-Gal promotes the toxic conversion of αSyn via aberrant interactions between αSyn and their substrate glycolipids, leading to the aggravation of αSyn-mediated neurodegeneration.
We have cloned and characterized a new diacylglycerol kinase (DGK) isozyme which is expressed in the retina and the brain of rat. The cDNA contains an open reading frame of 567 amino acid residues with a predicted protein of 64 kDa and shows very high homology to human DGKϵ. The new DGK isozyme contains two distinctive zinc‐finger structures and a putative catalytic domain. This DGK expressed predominantly in the inner and outer nuclear layers of retina. This expression pattern is different from those of the previously cloned DGKs including the human DGKϵ, suggesting that this DGK isozyme has potential importance in visual functions as was the case in Drosophila retinal cells.
Somatic sex determination in Drosophila depends on the expression of Sex-lethal ( Sxl ), whose level is determined by the relative number of X chromosomes and sets of autosomes (X:A ratio). The first step in regulation of Sxl expression is transcriptional control from its early promoter and several genes encoding transcription factors of the helix-loop-helix (HLH) family such as daughterless da,sisterless-b (sis-b), deadpan (dpn) and extramacrochaetae emc ) have been implicated. By the use of transfection assays and in vitro binding experiments, here we show that da/sis-b heterodimers bind several sites on the Sxl early promoter with different affinities and consequently tune the level of active transcription from this promoter. Interestingly, our data indicate that repression by the dpn product of da/sis-b dependent activation results from specific binding of dpn protein to a unique site within the promoter. This contrasts with the mode of emc repression, which inhibits the formation of the da/sis-b heterodimers. These results reveal the molecular mechanisms by which Sxl gene transcription is positively or negatively regulated to control somatic sex determination.
Public stigma against depression contributes to low employment rates among individuals with depression. Contact-based educational (CBE) interventions have been shown to reduce this public stigma.We investigated the ability of our Virtual Reality Antistigma (VRAS) app developed for CBE interventions to reduce the stigma of depression.Sixteen medical students were recruited and randomized 1:1 to the intervention group, who used the VRAS app (VRAS group), and the control group, who watched a video on depression. The depression stigma score was assessed using the Depression Stigma Scale (DSS) and Attitudinal Social Distance (ASD) questionnaire at pre- and postintervention. Feasibility was assessed in both groups and usability was assessed only in the VRAS group after the intervention. A qualitative study was performed on the acquisition of knowledge about stigma in both groups based on participants' answers to open-ended questions and interviews after the intervention.The feasibility score was significantly higher in the VRAS group (mean 5.63, SD 0.74) than in the control group (mean 3.88, SD 1.73; P=.03). However, no significant differences were apparent between the VRAS and control groups for the DSS (VRAS: mean 35.13, SD 5.30; control: mean 35.38, SD 4.50; P=.92) or ASD (VRAS: mean 12.25, SD 3.33; control: mean 11.25, SD 1.91; P=.92). Stigma scores tended to decrease; however, the stigma-reducing effects of the VRAS app were not significant for the DSS (pre: mean 33.00, SD 4.44; post: mean 35.13, SD 5.30; P=.12) or ASD (pre: mean 13.25, SD 3.92; post: mean 12.25, SD 3.33; P=.12). Qualitative analysis suggested that the VRAS app facilitated perspective-taking and promoted empathy toward the patient.The CBE intervention using virtual reality technology (VRAS app) was as effective as the video intervention. The results of the qualitative study suggested that the virtual reality intervention was able to promote perspective-taking and empathy toward patients.University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000043020; https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000049109.
