A combination of commercial and traditional food-source-derived enzymatic treatment acts as a potential tool to produce functional yuzu (Citrus junos) powder.

Enzymatic modifications have been applied in citrus to enhance their physicochemical and biological properties and reduce their bitterness. Notwithstanding, research on the combination of enzyme treatment of yuzu is lacking. In this study, yuzu was treated with a combination of isolated cellulase NY203, pectinase UF, and cellulase KN, and this enzymatic treatment was found to increase monosaccharide, naringenin, and hesperetin levels. In contrast, dietary fiber, cellulose, hemicellulose, lignin, and pectin levels were decreased. Moreover, the enzymes disintegrated the inner and outer surface structures and chemical bonding of yuzu, thus improving its solubility rate, water-holding capacity, oil-adsorption capacity, cholesterol-binding capacity, and water-swelling capacity. Furthermore, NY203 + UF + KN combination treatment reduced the bitterness of treated yuzu by 50 % compared with the control. Additionally, NY203 + UF + KN treatment yielded a 28 % decrease in lipid accumulation and two-fold higher lipolytic activity in 3T3L-1 adipocytes. These findings are potentially beneficial to the food/nutraceutical industries regarding functional yuzu powder production.

Core promoter activity contributes to chromatin-based regulation of internal cryptic promoters.

During RNA polymerase II (RNA Pol II) transcription, the chromatin structure undergoes dynamic changes, including opening and closing of the nucleosome to enhance transcription elongation and fidelity. These changes are mediated by transcription elongation factors, including Spt6, the FACT complex, and the Set2-Rpd3S HDAC pathway. These factors not only contribute to RNA Pol II elongation, reset the repressive chromatin structures after RNA Pol II has passed, thereby inhibiting aberrant transcription initiation from the internal cryptic promoters within gene bodies. Notably, the internal cryptic promoters of infrequently transcribed genes are sensitive to such chromatin-based regulation but those of hyperactive genes are not. To determine why, the weak core promoters of genes that generate cryptic transcripts in cells lacking transcription elongation factors (e.g. STE11) were replaced with those from more active genes. Interestingly, as core promoter activity increased, activation of internal cryptic promoter dropped. This associated with loss of active histone modifications at the internal cryptic promoter. Moreover, environmental changes and transcription elongation factor mutations that downregulated the core promoters of highly active genes concomitantly increased their cryptic transcription. We therefore propose that the chromatin-based regulation of internal cryptic promoters is mediated by core promoter strength as well as transcription elongation factors.

Physiochemical properties, dietary fibers, and functional characterization of three yuzu cultivars at five harvesting times.

This research focused on physiochemical and nutritional properties and functional characterization of three cultivars of yuzu-Native, Tadanishiki yuzu, and Namhae1-during different seasons. According to the cultivar and harvest time, yuzu cultivars were analyzed for free sugar, dietary fiber, hesperidin, naringin, and flavonoid content as well as antioxidant and antihypertensive activity. During November, Namhae1 exhibited the highest fruit weight, °Brix/acidity ratio, and total dietary fiber content. Tadanishiki contained the highest fructose and sucrose levels, pectin and cellulose contents, and soluble dietary fiber. Tadanishiki also had the highest hesperidin content in October, while the naringin content and antioxidant activity were the greatest in November. Antihypertensive activity was also the strongest for Tadanishiki, which was picked in October and November. These results indicated that Tadanishiki in October or November was the best for consumption or favorable processing because of its excellent product quality and high levels of nutritional and functional compounds.

Antioxidative and Analgesic Effects of Naringin through Selective Inhibition of Transient Receptor Potential Vanilloid Member 1.

Transient receptor potential vanilloid member 1 (TRPV1) is activated in response to capsaicin, protons, temperature, and free reactive oxygen species (ROS) released from inflammatory molecules after exposure to harmful stimuli. The expression level of TRPV1 is elevated in the dorsal root ganglion, and its activation through capsaicin and ROS mediates neuropathic pain in mice. Its expression is high in peripheral and central nervous systems. Although pain is a response evolved for survival, many studies have been conducted to develop analgesics, but no clear results have been reported. Here, we found that naringin selectively inhibited capsaicin-stimulated inward currents in Xenopus oocytes using a two-electrode voltage clamp. The results of this study showed that naringin has an IC50 value of 33.3 µM on TRPV1. The amino acid residues D471 and N628 of TRPV1 were involved in its binding to naringin. Our study bridged the gap between the pain suppression effect of TRPV1 and the preventive effect of naringin on neuropathic pain and oxidation. Naringin had the same characteristics as a model selective antagonist, which is claimed to be ideal for the development of analgesics targeting TRPV1. Thus, this study suggests the applicability of naringin as a novel analgesic candidate through antioxidative and analgesic effects of naringin.

NuA3 HAT antagonizes the Rpd3S and Rpd3L HDACs to optimize mRNA and lncRNA expression dynamics.

In yeast, NuA3 histone acetyltransferase (NuA3 HAT) promotes acetylation of histone H3 lysine 14 (H3K14) and transcription of a subset of genes through interaction between the Yng1 plant homeodomain (PHD) finger and H3K4me3. Although NuA3 HAT has multiple chromatin binding modules with distinct specificities, their interdependence and combinatorial actions in chromatin binding and transcription remain unknown. Modified peptide pulldown assays reveal that the Yng1 N-terminal region is important for the integrity of NuA3 HAT by mediating the interaction between core subunits and two methyl-binding proteins, Yng1 and Pdp3. We further uncover that NuA3 HAT contributes to the regulation of mRNA and lncRNA expression dynamics by antagonizing the histone deacetylases (HDACs) Rpd3S and Rpd3L. The Yng1 N-terminal region, the Nto1 PHD finger and Pdp3 are important for optimal induction of mRNA and lncRNA transcription repressed by the Set2-Rpd3S HDAC pathway, whereas the Yng1 PHD finger-H3K4me3 interaction affects transcriptional repression memory regulated by Rpd3L HDAC. These findings suggest that NuA3 HAT uses distinct chromatin readers to compete with two Rpd3-containing HDACs to optimize mRNA and lncRNA expression dynamics.

Transcription-dependent targeting of Hda1C to hyperactive genes mediates H4-specific deacetylation in yeast.

In yeast, Hda1 histone deacetylase complex (Hda1C) preferentially deacetylates histones H3 and H2B, and functionally interacts with Tup1 to repress transcription. However, previous studies identified global increases in histone H4 acetylation in cells lacking Hda1, a component of Hda1C. Here, we find that Hda1C binds to hyperactive genes, likely via the interaction between the Arb2 domain of Hda1 and RNA polymerase II. Additionally, we report that Hda1C specifically deacetylates H4, but not H3, at hyperactive genes to partially inhibit elongation. This role is contrast to that of the Set2-Rpd3S pathway deacetylating histones at infrequently transcribed genes. We also find that Hda1C deacetylates H3 at inactive genes to delay the kinetics of gene induction. Therefore, in addition to fine-tuning of transcriptional response via H3-specific deacetylation, Hda1C may modulate elongation by specifically deacetylating H4 at highly transcribed regions.

Rpd3L HDAC links H3K4me3 to transcriptional repression memory.

Transcriptional memory is critical for the faster reactivation of necessary genes upon environmental changes and requires that the genes were previously in an active state. However, whether transcriptional repression also displays 'memory' of the prior transcriptionally inactive state remains unknown. In this study, we show that transcriptional repression of ∼540 genes in yeast occurs much more rapidly if the genes have been previously repressed during carbon source shifts. This novel transcriptional response has been termed transcriptional repression memory (TREM). Interestingly, Rpd3L histone deacetylase (HDAC), targeted to active promoters induces TREM. Mutants for Rpd3L exhibit increased acetylation at active promoters and delay TREM significantly. Surprisingly, the interaction between H3K4me3 and Rpd3L via the Pho23 PHD finger is critical to promote histone deacetylation and TREM by Rpd3L. Therefore, we propose that an active mark, H3K4me3 enriched at active promoters, instructs Rpd3L HDAC to induce histone deacetylation and TREM.

Erratum: Modulation of mRNA and lncRNA expression dynamics by the Set2-Rpd3S pathway.

This corrects the article DOI: 10.1038/ncomms13534.

Fine-tuning of gene expression dynamics by the Set2-Rpd3S pathway.

RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects have been seen on genome-wide transcription under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes. Interestingly, a majority of Set2-repressed genes are overlapped by a lncRNA transcription that targets H3K36 methylation and deacetylation by Rpd3S HDAC to mRNA promoters. Furthermore, this pathway delays the induction of many cryptic transcripts upon environmental changes. Therefore, the Set2-Rpd3S HDAC pathway functions to fine-tune expression dynamics of mRNAs and ncRNAs. [BMB Reports 2017; 50(4): 162-163].

Modulation of mRNA and lncRNA expression dynamics by the Set2-Rpd3S pathway.

H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase. Here we show that the distance between an mRNA and overlapping lncRNA promoter determines whether Set2-Rpd3S or Set3C represses. This analysis also reveals many previously unreported cryptic ncRNAs induced by specific carbon sources, showing that cryptic promoters can be environmentally regulated. Therefore, in addition to repression of cryptic transcription and modulation of elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs and ncRNAs.

Physiological properties of Scomber japonicus meat hydrolysate prepared by subcritical water hydrolysis.

The health-beneficial biological activities, including antioxidant and tyrosinase inhibitory activities, of Scomber japonicus muscle protein hydrolysates prepared by subcritical water hydrolysis were investigated. After 5 min of subcritical hydrolysis at 140 degrees C, 59.76% of S. japonicus muscle protein was hydrolyzed, the highest degree of hydrolysis in all the groups were tested. According to the response surface methodology results, as the reaction temperature and reaction time became lower and shorter, the yield became higher. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity (90.63%) occurred in hydrolysates treated at 140 degrees C for 5 min, and the highest tyrosinase inhibitory activity (65.54%) was identified in hydrolysates treated at 200 degreesC for 15 min. Changes in the molecular weight distribution of S. japonicus muscle proteins after subcritical water hydrolysis were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Subcritical water hydrolysis is a suitable technique for obtaining S.japonicus muscle protein hydrolysates with useful biological activities, within a short time (5-15 min).

Inhibitory effects of seaweed extracts on the growth of the vaginal bacterium Gardnerella vaginalis.

Of 44 species of seaweed screened for potential anti-Gardnerella vaginalis activity, 27 (61.4%) showed antimicrobial activity by the agar disk-diffusion method. Among them, the strongest activities against the pathogen were exhibited by Chlorophyta, with Ulva pertusa producing an 11.3-mm zone of inhibition at 5 mg disk⁻¹. The MIC values of U. pertusa extracts against both G. vaginalis KCTC 5096 and KCTC 5097, the main cause of vaginosis, were 312 µg ml⁻¹, while the MIC values against both Candida albicans KCTC 7270 and KCTC 7965, the main cause of candidiasis, were 2.5 mg ml⁻¹. Against Lactobacillus gasseri KCTC 3173 and Lactobacillus jensenii KCTC 5194, members of the normal vaginal microflora, no inhibitory effect was seen even at 10 mg ml⁻¹. To identify the primary active compounds, a U. pertusa powder was successively fractionated according to polarity, and the main active agents against G. vaginalis KCTC 5096 were determined to be nitrogenous compounds (156 µg ml⁻¹ of the MIC value). According to these results, it was suggested that extracts of the seaweed U. pertusa are valuable for the development of natural therapeutic agents for treating women with bacterial vaginosis.

Seasonal variation of antibacterial activities in the green alga Ulva pertusa Kjellman.

The present study was performed to screen out the extracts of algae and assess the seasonal variation in antimicrobial activity of Ulva pertusa against Gardnerella vaginalis. Seasonal variation in antibacterial activity was observed, with the extracts showing no activity during summer and autumn, and showing antibacterial activity from early winter (December) to middle spring (April). The maximum value of antimicrobial activity (6.5 mm inhibition zone at 5 mg disk(-1)) of U. pertusa against G. vaginalis was observed in April. Otherwise, for both chlorophyll a and b, the highest content (2.87 mg g(-1) and 1.37 mg g(-1)) was observed in March 2009. These results may reflect variation in cellular chemical compositions such as secondary metabolite(s) rather than chlorophyll and biological activities according to season.

Antioxidative and anticancer activity of extracts of cherry (Prunus serrulata var. spontanea) blossoms.

Organic solvent (methanol, ethanol, and acetone) extracts and water extracts of cherry (Prunus serrulata var. spontanea) blossoms were prepared, and antioxidant activities of the extracts were evaluated. Methanolic CBE (100 microg/ml) showed the highest total phenol content (104.30 microM), radical scavenging activity (34.2%), and reducing power (0.391). The effect of CBE on DNA damage induced by H(2)O(2) in human leukocytes was evaluated by Comet assay. All CBE was a potent dose dependent inhibitor of DNA damage induced by 200 microM of H(2)O(2), methanolic CBE showed the most strong inhibition activity. The methanolic CBE of 500 microg/ml showed 38.8% inhibition against growth of human colon cancer cell line HT-29. These results indicated that cherry blossoms could provide valuable bioactive materials.