Multi-modal Representation of the Size of Space in the Human Brain.

To estimate the size of an indoor space, we must analyze the visual boundaries that limit the spatial extent and acoustic cues from reflected interior surfaces. We used fMRI to examine how the brain processes the geometric size of indoor scenes when various types of sensory cues are presented individually or together. Specifically, we asked whether the size of space is represented in a modality-specific way or in an integrative way that combines multimodal cues. In a block-design study, images or sounds that depict small- and large-sized indoor spaces were presented. Visual stimuli were real-world pictures of empty spaces that were small or large. Auditory stimuli were sounds convolved with different reverberations. By using a multivoxel pattern classifier, we asked whether the two sizes of space can be classified in visual, auditory, and visual-auditory combined conditions. We identified both sensory-specific and multimodal representations of the size of space. To further investigate the nature of the multimodal region, we specifically examined whether it contained multimodal information in a coexistent or integrated form. We found that angular gyrus and the right medial frontal gyrus had modality-integrated representation, displaying sensitivity to the match in the spatial size information conveyed through image and sound. Background functional connectivity analysis further demonstrated that the connection between sensory-specific regions and modality-integrated regions increases in the multimodal condition compared with single modality conditions. Our results suggest that spatial size perception relies on both sensory-specific and multimodal representations, as well as their interplay during multimodal perception.

Valorization of leftover green tea residues through conversion to bioactive peptides using probiotics-aided anaerobic digestion.

Bioactive peptides (BPs) are protein fragments that benefit human health. To assess whether leftover green tea residues (GTRs) can serve as a resource for new BPs, we performed in silico proteolysis of GTRs using the BIOPEP database, revealing a wide range of BPs embedded in GTRs. Comparative genomics and the percentage of conserved protein analyses enabled us to select a few probiotic strains for GTR hydrolysis. The selected probiotics digested GTRs anaerobically to yield GTR-derived peptide fractions. To examine whether green tea (GT) peptide fractions could be potential mediators of host-microbe interactions, we comprehensively screened agonistic and antagonistic activities of 168 human G protein-coupled receptors (GPCRs). NanoLC-MS/MS analysis and thin-layer chromatography allowed the identification of peptide sequences and the composition of glycan moieties in the GTRs. Remarkably, GT peptide fractions produced by Lactiplantibacillus plantarum APsulloc 331261, a strain isolated from GT, showed a potent-binding activity for P2RY6, a GPCR involved in intestinal homeostasis. Therefore, this study suggests the potential use of probiotics-aided GTR hydrolysates as postbiotic BPs, providing a biological process for recycling GTRs from agro-waste into renewable resources as health-promoting BPs.

Astaxanthin Inhibits Oxidative Stress-Induced Ku Protein Degradation and Apoptosis in Gastric Epithelial Cells.

Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells. Therefore, astaxanthin may inhibit oxidative stress-induced DNA damage by preventing Ku protein degradation and thereby suppressing apoptosis. Ku proteins can be degraded via ubiquitination and neddylation which adds ubiquitin-like protein to substrate proteins. We aimed to determine whether oxidative stress decreases Ku70/80 expression through the ubiquitin-proteasome pathway to induce apoptosis and whether astaxanthin inhibits oxidative stress-induced changes in gastric epithelial AGS cells. We induced oxidative stress caused by the treatment of ß-D-glucose (G) and glucose oxidase (GO) in the cells. As a result, the G/GO treatment increased ROS levels, decreased nuclear Ku protein levels and Ku-DNA-binding activity, and induced the ubiquitination of Ku80. G/GO increased the DNA damage marker levels (γ-H2AX; DNA fragmentation) and apoptosis marker annexin V-positive cells and cell death. Astaxanthin inhibited G/GO-induced alterations, including Ku degradation in AGS cells. MLN4924, a neddylation inhibitor, and MG132, a proteasome inhibitor, suppressed G/GO-mediated DNA fragmentation and decreased cell viability. These results indicated that G/GO-induced oxidative stress causes Ku protein loss through the ubiquitin-proteasome pathway, resulting in DNA fragmentation and apoptotic cell death. Astaxanthin inhibited oxidative stress-mediated apoptosis via the reduction of ROS levels and inhibition of Ku protein degradation. In conclusion, dietary astaxanthin supplementation or astaxanthin-rich food consumption may be effective for preventing or delaying oxidative stress-mediated cell damage by suppressing Ku protein loss and apoptosis in gastric epithelial cells.

Identification and molecular study on the interaction of Schisandrin C with human 5-HT3A receptor.

Schisandrin C (Sch C) is one of the main components of Schisandra chinensis (Schisandra). Since the olden times, Schisandra has been used as a traditional herbal medicine in Asia. Recent studies have shown that Schisandra is effective against irritable bowel syndrome (IBS) in an animal model and affects IBS through the 5-HT3A pathway in the IBS rat model. However, there lacks fundamental research on the interaction of specific components of Schisandra with the 5-HT3A receptor for the treatment of IBS. We hypothesized that a component of Schisandra binds to the 5-HT3A receptor and identified Sch C via a screening work using two electrode-voltage clamps (TEVC). Thus, we aimed to elucidate the neuropharmacological actions between Sch C and the 5-HT3A receptor at molecular and cellular levels. Co-treatment of Sch C with 5-HT inhibited I5-HT in a reversible, concentrate-dependent, like-competition, and voltage-independent manner, and IC50 values of Sch C. Besides, the main binding positions of Sch C were identified through 3D modeling and point mutation were V225A and V288Y on 5-HT3A receptor. Thus, we suggest the potential of Sch C in treating IBS in a manner that suppresses excessive neuronal serotonin signaling in the synapse of sensory neurons and enterochromaffin (EC) cells. In conclusion, the results demonstrate the mechanism of interaction between Sch C and 5-HT3A receptor and reveal Sch C as a novel antagonist.

Moderated Mediation Effect of Mindfulness on the Relationship Between Muscular Skeletal Disease, Job Stress, and Turnover Among Korean Firefighters.

BACKGROUND: This study investigated the effect of increased job stress, caused by musculoskeletal disease (MSD) among firefighters, on a firefighter's intention to leave the profession, henceforth referred to as "turnover intention," and verified the moderating effect of mindfulness on such a relationship. METHODS: A survey involving a total of 549 Korean male firefighters as participants was conducted herein, and the following results were obtained: the mediation effect of the MSD to turnover intention through job stress was confirmed, and the indirect effect of job stress was verified. RESULTS: We verified the moderated mediation effect of mindfulness on the relation:MSD, job stress, and turnover intention. The conditional indirect effect for middle and high levels of mindfulness is significant. CONCLUSION: The result of this study is supported by proofs of the relationship between a firefighter's MSD, job stress, and turnover intention, and these case studies reveal the moderated mediation effect of dispositional mindfulness.

Regulation of p21 expression for anti-apoptotic activity of DDX3 against sanguinarine-induced cell death on intrinsic pathway.

BACKGROUND: DDX3 plays a role in multicellular pathways, especially exerting an anti-apoptotic effect on extrinsic apoptosis. However, studies on the role of DDX3 in intrinsic apoptosis are lacking. PURPOSE: In this study, we aimed to study the bio-function of DDX3 anti-apoptotic activity in the intrinsic pathway using HeLa cells treated with sanguinarine. STUDY DESIGN: Screening of apoptosis-inducing agents found that sanguinarine was the most effective. After treatment with sanguinarine, cell viability, caspase-3 activity, and intrinsic gene expression were analyzed. FACS assays were used to analyze the effect of overexpression and knockdown of DDX3 to determine its role on intrinsic apoptosis. The relationship between DDX3 and the inhibition of p21 and apoptosis was investigated. RESULTS: Sanguinarine was determined to be the most effective intrinsic apoptosis-inducing agent in HeLa cervical cancer cells. DDX3 upregulated anti-apoptotic gene expression (Bcl-xL, cyclin D1, cyclin E, and cyclin B1) and downregulated pro-apoptotic gene expression (caspase-3, Bax) after sanguinarine treatment. The apoptotic cell death rate increased from 8.74% (sanguinarine-treated control) to 17.6% after the knockdown of DDX3 but decreased to 5.29% after DDX3 overexpression. The results implied that p21 might be involved in the toxicity of sanguinarine to HeLa cells. Overexpression and knockdown of DDX3 under sanguinarine-treated conditions showed that DDX3 inhibited p21 expression in sanguinarine-treated HeLa cells. Notably, when we tested p21 expression among eight mutants located in the functional residues of DDX3 (S90A, S90E, T204A, T204E, GET, NEAD, LAT, and HRISR) under sanguinarine-treated conditions, only the S90E mutation in DDX3 had an effect on the inhibition of p21 expression and levels of pro-apoptotic genes (Bax and caspase-3) and anti-apoptotic genes (Bcl-xL, cyclin D1, cyclin E, and cyclin B1), as well as DDX3. CONCLUSION: Taken together, the results suggest that the S90E residue is important for the regulation of p21 expression responsible for the anti-apoptotic activity of DDX3 in HeLa cells treated with sanguinarine. A model of the antiapoptotic function of DDX3 on sanguinarine-treated HeLa cells was proposed to understand the molecular mechanism of the intrinsic apoptosis inhibition in cervical cancer cells.

Effects of Sumsu (Bufonis venenum) Pharmacopuncture Treatment on Depression in Mice.

OBJECTIVES: The main objective of this study was to evaluate the anti-depressant effects of pharmacopuncture using sumsu (Bufonis venenum). METHODS: Animals were divided into three groups (control, sham, and experimental), with eight mice per group. The sham and the experimental groups were exposed to 2 hours of immobilization stress daily for 14 days. They were also injected with normal saline (sham) or subjected to pharmacopuncture with sumsu at the acupoints HT7, SP6, and GV20 (experimental). The depression or anxiety-like behaviors of the mice in each group were evaluated 1 day after treatment. RESULTS: There was no difference in locomotor activity between the groups during the open-field test; i.e., all groups had normal motor function. However, the open-field and the forced-swimming tests revealed that depression and anxiety-like behaviors were decreased significantly in the group treated with sumsu pharmacopuncture. CONCLUSION: Sumsu pharmacopuncture attenuated depressive or anxiety-like behavior in mice stressed with chronic immobilization. These results suggest that sumsu pharmacopuncture has therapeutic potential for treating neuropsychiatric disorders such as anxiety or depression disorder.

Does the effect of acupuncture depend on needling sensation and manipulation?

BACKGROUND: Acupuncture sensation and manipulation have been considered to be an important component of acupuncture in traditional Asian medicine. However, there has been limited research as to whether acupuncture sensation is associated with therapeutic benefit. This study investigated the relationship between acupuncture sensation and analgesic effect according to acupuncture manipulation. METHOD: Fifty-three healthy volunteers received three different forms of acupuncture in a single-blinded crossover design: superficial needling (0.3 cm), deep needling (2 cm) and needling with bi-directional rotation. The effects of acupuncture were evaluated by using the pressure pain threshold. Acupuncture sensation measurement was done in two ways. RESULTS: Both total acupuncture sensation and increase of the pressure pain threshold were maximum in needling with rotation, followed by deep needling and superficial needling. Repeated-measure analysis of variance (ANOVA) analysis was carried out to assess whether there was a significant difference; both showed significant difference (p = 0.000, 0.003). A paired sample t-test was carried out, which revealed that needling with rotation showed significant difference from both superficial needling and deep needling. Further, the correlation between the total acupuncture sensation and changes in pressure pain threshold were calculated using Pearson correlation; there was a significant correlation (p = 0.002, p = 0.013). CONCLUSION: Acupuncture sensation and pressure pain threshold increase according to the depth and rotation of acupuncture. Especially, both display significant increase with needle rotation. Further, there is a significant correlation between acupuncture needling sensation and increase in pressure pain threshold. It seems that needle rotation and acupuncture sensation play an important role in verifying the effect of acupuncture.

Rice mitogen-activated protein kinase interactome analysis using the yeast two-hybrid system.

Mitogen-activated protein kinase (MAPK) cascades support the flow of extracellular signals to intracellular target molecules and ultimately drive a diverse array of physiological functions in cells, tissues, and organisms by interacting with other proteins. Yet, our knowledge of the global physical MAPK interactome in plants remains largely fragmented. Here, we utilized the yeast two-hybrid system and coimmunoprecipitation, pull-down, bimolecular fluorescence complementation, subcellular localization, and kinase assay experiments in the model crop rice (Oryza sativa) to systematically map what is to our knowledge the first plant MAPK-interacting proteins. We identified 80 nonredundant interacting protein pairs (74 nonredundant interactors) for rice MAPKs and elucidated the novel proteome-wide network of MAPK interactors. The established interactome contains four membrane-associated proteins, seven MAP2Ks (for MAPK kinase), four MAPKs, and 59 putative substrates, including 18 transcription factors. Several interactors were also validated by experimental approaches (in vivo and in vitro) and literature survey. Our results highlight the importance of OsMPK1, an ortholog of tobacco (Nicotiana benthamiana) salicyclic acid-induced protein kinase and Arabidopsis (Arabidopsis thaliana) AtMPK6, among the rice MAPKs, as it alone interacts with 41 unique proteins (51.2% of the mapped MAPK interaction network). Additionally, Gene Ontology classification of interacting proteins into 34 functional categories suggested MAPK participation in diverse physiological functions. Together, the results obtained essentially enhance our knowledge of the MAPK-interacting protein network and provide a valuable research resource for developing a nearly complete map of the rice MAPK interactome.

Screening of Korean Medicinal Plant Extracts for α-Glucosidase Inhibitory Activities.

Glycosidases are the enzymes involved in various biochemical processes related to metabolic disorders and diseases. Therefore, much effort has been focused on searching novel pharmacotherapy for the treatment of these ailments from medicinal plants due to higher safety margins. To pursue these efforts, the present study was performed to evaluate the α-glucosidase inhibitory activities of thirty Korean medicinal plant extracts. Among the plants studied, Euonymus sachalinensis, Rhododendron schlippenbachii, Astilbe chinensis and Juglans regia showed the strongest α-glucosidase inhibitory activity with IC50 values of 10, 20, 30 and 80 µg/mL, respectively. In addition, Meliosma oldhamii and Symplocos chinensis showed moderate α-glucosidase inhibition with IC50 values of 150 and 220 µg/mL, respectively. Therefore, they might prove to be a potential natural source for the treatment of metabolic ailments such as, diabetes, and need further investigations.

A tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity.

The human lysyl oxidase-like 3 (LOXL3) encodes a member of the emerging family of lysyl oxidase (LOX) that functions as a copper-dependent amine oxidase. The LOXL3 protein contains four scavenger receptor cysteine-rich domains in the N terminus in addition to the C-terminal characteristic domains of the LOX family, such as a copper binding domain, a cytokine receptor-like domain and residues for the lysyl-tyrosyl quinone cofactor. Using BLASTN searches, we identified a LOXL3 variant LOXL3-sv1 that lacked the sequences corresponding to exons 1, 2, 3, and 5 of LOXL3. LOXL3-sv1 showed an exon-intron structure distinct from LOXL3, additionally containing an 80-bp sequence corresponding to intron 3 of LOXL3 in the 5'-UTR and a 561-bp sequence corresponding to the 3'-flanking genomic region of exon 14 in the 3'-UTR. LOXL3-sv1 was predicted to encode a polypeptide of 392 amino acids that contains the C-terminal domains required for amine oxidase activity but lacks the N-terminal SRCR domains 1, 2, and 3. The recombinant LOXL3-sv1 protein showed a beta-aminopropionitrile-inhibitable amine oxidase activity toward elastin and collagen with substrate specificity. In RT-PCR assays with various human tissues, LOXL3-sv1 and LOXL3 showed distinct expression patterns. Further, luciferase reporter assays revealed a strong promoter element in intron 3 that probably functions as a regulatory region for the expression of LOXL3-sv1. These findings strongly indicate that LOXL3 encodes two variants, LOXL3 and LOXL3-sv1, both of which function as amine oxidases with distinct tissue and substrate specificities from one another.