Modified Egocentric Viewpoint for Softer Seated Experience in Virtual Reality.

Users in a prolonged experience of virtual reality adopt a sitting position according to their task, as they do in the real world. However, inconsistencies in the haptic feedback from a chair they sit on in the real world and that which is expected in the virtual world decrease the feeling of presence. We aimed to change the perceived haptic features of a chair by shifting the position and angle of the users' viewpoints in the virtual reality environment. The targeted features in this study were seat softness and backrest flexibility. To enhance the seat softness, we shifted the virtual viewpoint using an exponential formula soon after a user's bottom contacted the seat surface. The flexibility of the backrest was manipulated by moving the viewpoint, which followed the tilt of the virtual backrest. These shifts make users feel as if their body moves along with the viewpoint; as a result, they would perceive pseudo-softness or flexibility consistently with the body movement. Based on subjective evaluations, we confirmed that the participants perceived the seat as being softer and the backrest as being more flexible than the actual ones. These results demonstrated that only shifting the viewpoint could change the participants' perceptions of the haptic features of their seats, although significant changes created strong discomfort.

Top-down effect of body representation on pain perception.

Many studies on body representation intend to change the perceived size, material, and structure of the body. However, whether the perception of a stimulus can be modified by manipulating body representation remains largely unexplored. Thus, the current study investigated the relationship between transparency of body representation and pain perception. Using augmented reality technology, we made the participants' limbs transparent and analyzed changes in body representation. Using a questionnaire, we confirmed that the participants perceived their limb as transparent. Simultaneously, their sense of ownership of the limb decreased, because they felt that it no longer belonged to their body. The participants were given an electrical stimulus to assess their subjective perception of pain intensity. An increase in limb opacity decreased the perception of pain, which, in turn, increased the feeling of transparency. These results suggested that the feeling of transparency in their limb favored the decrease in perceived pain. This effect was modified by body ownership, where high levels reinforced the analgesic effect. However, body ownership displayed a positive relationship with perceived pain. The study suggests that body transparency may constitute a strategy for decreasing refractory pain given that body ownership is retained at a high level.

Health Effects of Drinking Water Produced from Deep Sea Water: A Randomized Double-Blind Controlled Trial.

Global trends focus on a balanced intake of foods and beverages to maintain health. Drinking water (MIU; hardness = 88) produced from deep sea water (DSW) collected offshore of Muroto, Japan, is considered healthy. We previously reported that the DSW-based drinking water (RDSW; hardness = 1000) improved human gut health. The aim of this randomized double-blind controlled trial was to assess the effects of MIU on human health. Volunteers were assigned to MIU (n = 41) or mineral water (control) groups (n = 41). Participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire was administered, and stool and urine samples were collected throughout the intervention. We measured the fecal biomarkers of nine short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA), as well as urinary isoflavones. In the MIU group, concentrations of three major SCFAs and sIgA increased postintervention. MIU intake significantly affected one SCFA (butyric acid). The metabolic efficiency of daidzein-to-equol conversion was significantly higher in the MIU group than in the control group throughout the intervention. MIU intake reflected the intestinal environment through increased production of three major SCFAs and sIgA, and accelerated daidzein-to-equol metabolic conversion, suggesting the beneficial health effects of MIU.

Helicobacter pylori protein that binds to and activates platelet specifically reacts with sera of H. pylori-associated chronic immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antiplatelet antibodies and/or CD8 + T cells, resulting in the destruction of platelets and decreased platelet counts. Helicobacter pylori that persistently colonizes the stomach causes various disorders, including extragastric diseases such as chronic ITP (cITP). Several studies have reported increased platelet counts in H. pylori-infected cITP patients with eradication treatment and also the pathophysiological pathways involving cross-reaction of antibodies against H. pylori with platelets, the modulation of Fcrγ receptors balance and others. We previously reported an immunocomplex pathway comprising H. pylori low-molecular-weight (LMW) antigens, their antibodies, and platelets, involved in the development of H. pylori-associated cITP; however, the LMW antigens were not identified. In the present study, we demonstrated that the H. pylori LMW antigen of the immunocomplex was identified as Lpp20 of outer membrane proteins. Lpp20 could bind to platelets and specifically react with sera of H. pylori-associated cITP patients.

Hot-Cold Confusion: Inverse Thermal Sensation When Hot and Cold Stimuli Coexist in a Thermal Localization Task.

We focused on the inverse thermal sensation caused by the presence of both hot and cold stimuli, which we named hot-cold confusion. Some researchers have shown that when participants touch a thermal stimulus simultaneously with two opposite thermal stimuli on both sides, the outer temperatures dominate the center temperature; for example, a hot stimulus between two cold stimuli is perceived as cold. However, there has not been sufficient research on the effect of the center stimulus on the outer stimuli. In the current study, we placed a participant's forearm on an alignment where hot and cold stimuli were alternately placed in three locations and found that the participants sometimes selected the inverse thermal sensation of the presented surface not only at the center but also at the outer locations. Namely, opposite thermal stimuli applied at multiple locations affected each other, and the participants sometimes perceived the hot stimulus at the outer location as cold even when the two of three stimuli were hot, and vice versa. In addition, using various alignments of thermal stimuli, we revealed a directional bias of the effect from the cold stimulus and a difference in strength according to its location on the forearm.

Drinking Refined Deep-Sea Water Improves the Gut Ecosystem with Beneficial Effects on Intestinal Health in Humans: A Randomized Double-Blind Controlled Trial.

World health trends are focusing on a balanced food and beverage intake for healthy life. Refined deep-sea water (RDSW), obtained from deep-sea water collected offshore in Muroto (Japan), is mineral-rich drinking water. We previously reported that drinking RDSW improves human gut health. Here, we analyzed the effect of drinking RDSW on the gut ecosystem to understand this effect. This was a randomized double-blind controlled trial. Ninety-eight healthy adults were divided into two groups: RDSW or mineral water (control). The participants consumed 1 L of either water type daily for 12 weeks. A self-administered questionnaire and stool and urine samples were collected through the intervention. The following were determined: fecal biomarkers of secretory immunoglobulin A (sIgA), five putrefactive products, and nine short-chain-fatty-acids (SCFAs) as the primary outcomes; and three urinary isoflavones and the questionnaire as secondary outcomes. In post-intervention in the RDSW group, we found increased concentrations of five SCFAs and decreased concentrations of phenol and sIgA (p < 0.05). The multiple logistic analysis demonstrated that RDSW significantly affected two biomarkers (acetic and 3-methylbutanoic acids) of the five SCFAs mentioned above (p < 0.05). Similarly, the concentrations of urinary isoflavones tended to increase in post-intervention in the RDSW group. Constipation was significantly alleviated in the RDSW group (94%) compared with the control group (60%). Drinking RDSW improves the intestinal environment, increasing fecal SCFAs and urinary isoflavones, which leads to broad beneficial effects in human.

MicroRNA-150 suppresses p27Kip1 expression and promotes cell proliferation in HeLa human cervical cancer cells.

MicroRNAs (miRNAs) exert critical roles in the majority of biological and pathological processes. Recent studies have associated miR-150 with a number of different cancer types. However, little is known about miR-150 targets in cervical cancer. In the present study, the HeLa human cervical cancer cell line was transfected with hsa-miR-150-5p mimics, hsa-miR-150-5p inhibitors or miRNA controls. miR-150 was predicted to bind the 3'untranslated region (3'UTR) of the CDKN1B gene, which encodes the cyclin-dependent kinase inhibitor 1B (p27Kip1). The direct binding between miR-150 and the 3'UTR of CDKN1B was confirmed using dual-luciferase reporter assays. The effects of miR-150 on CDKN1B mRNA expression, p27Kip1 protein expression, cell cycle and cell proliferation were determined using reverse-transcription quantitative PCR, western blot analysis, flow cytometry and WST-8 assays, respectively. miR-150 was demonstrated to directly target the 3'UTR of CDKN1B in transfected HeLa cells. The expression of CDKN1B mRNA and p27Kip1 protein was reduced by miR-150 mimics, and increased by miR-150 inhibitors. Moreover, the overexpression of miR-150 promoted cell cycle progression from the G0/G1 to the S phase and led to a significant increase in HeLa cell proliferation. The results of the present study indicated that miR-150 promotes HeLa cell cycle progression and proliferation via the suppression of p27Kip1 expression.

FIR haplodeficiency promotes splicing to pyruvate kinase M2 in mice thymic lymphoma tissues revealed by six-plex tandem mass tag quantitative proteomic analysis.

The switch of pyruvate kinase (PK) M1 to PKM2 is pivotal for glucose metabolism in cancers. The PKM1/M2 shift is controlled by the alternative splicing of two mutually exclusive exons in the PKM gene. PKM1 is expressed in differentiated tissues, whereas PKM2 is expressed in cancer tissues. This study revealed that the haplodeficiency of FUSE-binding protein (FBP)-interacting repressor (FIR), a transcriptional repressor of the c-myc gene, contributed to the splicing of PKM1 to PKM2 in mice thymic lymphoma and/or T-cell type acute lymphoblastic leukemia (T-ALL) using six-plex tandem mass tag (TMT) quantitative proteomic analysis. TMT revealed 648 proteins that were up- or downregulated in mice thymic lymphoma tissues compared with wild type mouse. These proteins included transcription factors and proteins involved in DNA damage repair, DNA replication, T-cell activation/proliferation, apoptosis, etc. Among them, PKM2 protein, but not PKM1, was upregulated in the thymic lymphoma as well as T-ALL. Using qRT-PCR, we revealed that the activation of PKM2 mRNA was higher in thymic lymphoma cells of FIR+/-TP53-/- mice than that in control lymphocytes of FIR+/+TP53-/- sorted by flow cytometry. FIR knockdown by siRNA suppressed hnRNPA1 expression in HeLa cells. These results indicated that FIR haplodeficiency contributes the alternative splicing of PKM1 to PKM2 by partly inhibiting hnRNPA1 expression in the thymic lymphoma cells prior to T-ALL. Taken together, our findings suggest that FIR and its related spliceosomes are potential therapeutic targets for cancers, including T-ALL.

[Alternative Splicing Detection as a Biomarker for Cancer Diagnosis: A Novel Progressive Mechanism of Acute Lymphoblastic Leukemia with Alternative Splicing as a Biomarker Candidate].

Alternative splicing is an important mechanism that links to transcription and contributes to protein diversity. Disturbed alternative splicing is frequently observed in cancers, but its precise mechanism remains largely unknown. FUSE-binding protein (FBP) -interacting repressor (FIR) is a transcriptional repressor of the c-myc gene. Previous studies indicated that a splice variant of FIR, FIRΔexon2, that lacks exon2 in the transcriptional repressor domain, was increased in colorectal cancers, hepatocellular carcinomas, and leukemia cells. Furthermore, FIRΔexon2 activated c-myc transcription by disabling wild-type FIR as a dominant-negative form of FIR. Recently, somatic mutations of the SF3B1 (SAP155) gene, a subunit of the SF3B spliceosome complex, were found in myelodysplastic leukemia. In this study, FIR heterozygous knockout (FIR(+/-)) was established as a dominant-negative model of FIR in the C57BL/6 mouse. FIR(+/-) mice showed an increased c-myc mRNA expression level, particularly in peripheral blood, although FIR(+/-) mice had no apparent pathogenic phenotype. Therefore, an increased c-myc mRNA expression level alone is not enough for leukemogenesis. Nevertheless, FIR(+/-)TP53(-/-) mice generated acute T-cell lymphoblastic leukemia (T-ALL) with increased organ and/or bone marrow invasion. In conclusion, alternative splicing of FIR, generating FIRΔexon2, contributes to not only colorectal carcinogenesis but also leukemogenesis independent of the c-Myc activation pathway. Finally, we will discuss our hypothesis that FIRΔexon2 interferes with FBW7, that FIRΔexon2 inhibits PP1 in the EGFR pathway, and that FIR haploinsufficiency is potentially associated with protein expression through transcriptional and post-transcriptional mechanisms.

The application of a three-step serum proteome analysis for the discovery and identification of novel biomarkers of hepatocellular carcinoma.

The representative tumor markers for HCC, AFP, and PIVKA-II are not satisfactory in terms of sensitivity and specificity in the early diagnosis of HCC. In search for novel markers for HCC, three-step proteome analyses were carried out in serum samples obtained from 12 patients with HCC and 10 with LC. As a first step, serum samples were subjected to antibody-based immunoaffinity column system that simultaneously removes twelve of abundant serum proteins. The concentrated flow-through was then fractionated using reversed-phase HPLC. Proteins obtained in each fraction were separated by SDS-PAGE. Serum samples obtained from patient with HCC and with LC were analyzed in parallel and their protein expression patterns were compared. A total of 83 protein bands were found to be upregulated in HCC serum. All the protein bands, the intensity of which was different between HCC and LC groups, were identified. Among them, clusterin was most significantly overexpressed (P = 0.023). The overexpression of serum clusterin was confirmed by ELISA using another validation set of HCC samples. Furthermore, serum clusterin was elevated in 40% of HCC cases in which both AFP and PIVKA-II were within their cut-off values. These results suggested that clusterin is a potential novel serum marker for HCC.