The CAPRICE (CPC) transcription factor regulates root hair initiation and inhibits trichome formation in Arabidopsis thaliana. CPC transits between root epidermal cells via its N-terminal S1 motif; however, the contribut...The CAPRICE (CPC) transcription factor regulates root hair initiation and inhibits trichome formation in Arabidopsis thaliana. CPC transits between root epidermal cells via its N-terminal S1 motif; however, the contribution of individual amino acid residues of this motif remains unclear. We generated seven CPC variants with alanine substitutions at positions 2-4 of the S1 motif and analyzed their functions in transgenic Arabidopsis. All variants promoted root hair initiation and inhibited trichome formation with reduced GL2 expression. Confocal imaging of green fluorescent protein-tagged proteins revealed partial reduction in their cell-to-cell movement compared with that of CPC wild-type. Protein structural analysis suggested that the biochemical properties of Phe-2, Arg-3, and Ser-4 within the disordered N-terminal region may contribute to CPC transport. These findings indicate that the S1 motif fine-tunes the intercellular mobility of CPC without compromising epidermal cell differentiation in the root epidermis.
The structural basis for dipeptides modulating PPARα remains unclear. AlphaFold2 identified Ile-His as a candidate predicted to interact with a novel alternative binding site. In HepG2 cells, Ile-His and Phe-Ala reduced...The structural basis for dipeptides modulating PPARα remains unclear. AlphaFold2 identified Ile-His as a candidate predicted to interact with a novel alternative binding site. In HepG2 cells, Ile-His and Phe-Ala reduced cholesterol accumulation, whereas Ala-Pro had no effect. These findings support the utility of structure-based prediction as a hypothesis-generating approach for identifying dipeptides associated with PPARα-related modulation of lipid metabolism.
Sweet potatoes were cultivated in hydroponics with low nitrogen fertilization. Through 16S rRNA gene amplicon sequencing, the most abundant genera in their storage roots were identified as Azospirillum, Sphingomonas, Bur...Sweet potatoes were cultivated in hydroponics with low nitrogen fertilization. Through 16S rRNA gene amplicon sequencing, the most abundant genera in their storage roots were identified as Azospirillum, Sphingomonas, Burkholderia, Bradyrhizobium, and Arthrobacter, all of which have been reported as nitrogen-fixing bacteria. These results suggest that nitrogen-fixing bacteria may selectively increase to compensate for insufficient nitrogen fertilization.
Dietary fiber may improve dysbiosis and contribute to the management of intestinal inflammation and muscle wasting. We examined whether low- and high-fermentable fibers differently influence dextran sulfate sodium (DSS)-...Dietary fiber may improve dysbiosis and contribute to the management of intestinal inflammation and muscle wasting. We examined whether low- and high-fermentable fibers differently influence dextran sulfate sodium (DSS)-induced colitis severity and muscle wasting. Male C57BL/6 J mice were assigned to four groups: nonfiber control (N), nonfiber with DSS (ND), cellulose with DSS (CD), and partially hydrolyzed guar-gum with DSS (GD), then subjected to a 27-day DSS protocol. Colitis severity was attenuated in the CD group, accompanied by increased Lactobacillus and Lactococcus lactis and decreased Clostridium innocuum group. These microbial changes were associated with maintenance of gastrocnemius muscle mass through mitochondrial biogenesis. Conversely, the GD group exhibited exacerbated colitis, associated with increased cecal succinate and expansion of Bacteroides, Blautia, and Enterococcaceae. These alterations correlated with muscle wasting accompanied by mitochondrial dysfunction. These results suggest that fiber fermentability plays a pivotal role in colitis management via gut microbiota alterations, also associated with muscle wasting.
Gibberellins (GAs) are a class of diterpenoid compounds that were originally identified as the causal toxins of rice seedling disease. GAs are phytohormones produced universally by plants, and more than 130 GAs have been...Gibberellins (GAs) are a class of diterpenoid compounds that were originally identified as the causal toxins of rice seedling disease. GAs are phytohormones produced universally by plants, and more than 130 GAs have been isolated to date. Studies using rice and Arabidopsis have revealed the biosynthesis and inactivation pathways of GAs as well as their signaling mechanisms. However, as genome sequencing progressed, it was found that mosses, liverworts, and hornworts lack certain genes encoding GA biosynthetic enzymes. Recent studies have revealed that partial GA biosynthetic pathways function in planta to biosynthesize bioactive substances that can be regarded as ancestral GA substances and to regulate their own growth. This review summarizes the current knowledge regarding the biosynthetic pathways of GA and ancestral GA substances.
Using a reporter assay system we screened a library of 472 compounds, and identified 1,25(OH)2D3, all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid, 17-allylamino-17-demethoxygeldanamycin, cantharidin, a...Using a reporter assay system we screened a library of 472 compounds, and identified 1,25(OH)2D3, all-trans-retinoic acid, 9-cis-retinoic acid, 13-cis-retinoic acid, 17-allylamino-17-demethoxygeldanamycin, cantharidin, and magnolol that inhibit FOXO1/3a activity. These compounds suppressed the increase in Atrogin1 gene expression induced by dexamethasone in C2C12 myoblasts. Therefore, these compounds may prevent muscle atrophy by inhibiting FOXO1/3a activity.
The gut microbiota plays a pivotal role in human health and interacts with quercetin, which undergoes extensive glucuronidation in the host organism. Microbial β-glucuronidases can deconjugate quercetin monoglucuronides,...The gut microbiota plays a pivotal role in human health and interacts with quercetin, which undergoes extensive glucuronidation in the host organism. Microbial β-glucuronidases can deconjugate quercetin monoglucuronides, regenerating the aglycone and modulating bioavailability; however, the magnitude and drivers of inter-individual variability remain unclear. We assembled a panel of human-derived intestinal isolates and quantified the deglucuronidation of four regioisomeric quercetin monoglucuronides using intact whole cells. Deglucuronidation capacity varied by approximately an order of magnitude across taxa and depended on the conjugation site: A/C-ring glucuronides were generally more labile than B-ring forms, with some species-specific exceptions. Notably, Faecalibacterium duncaniae emerged as a high-efficiency, broad-coverage deglucuronidator, outperforming the other isolates across all substrates. Whole-community assays of cecal content and fecal pellets echoed these preferences and revealed higher activity in digesta. These findings delineate species-resolved deglucuronidation patterns underlying inter-individual differences in quercetin bioavailability and identify species microbiota-driven deconjugation into pharmacokinetic models.
We investigated whether an endoplasmic reticulum (ER) stress-inducing chemical tunicamycin (TM) modulates bile acid (BA) metabolism in rats. Male Wistar rats were intraperitoneally administered TM at 0.1 mg/kg body weigh...We investigated whether an endoplasmic reticulum (ER) stress-inducing chemical tunicamycin (TM) modulates bile acid (BA) metabolism in rats. Male Wistar rats were intraperitoneally administered TM at 0.1 mg/kg body weight or vehicle, and samples were collected 2 days post-treatment. TM administration induced the levels of hepatic ER stress-related proteins. Increases were observed in both 12-hydroxylated and non-12-hydroxylated BA concentrations in the aortic plasma of the rats with TM treatment. Hepatic expression of Abcc3 that encodes BA transporter was significantly upregulated and positively correlated with the aortic BA levels. While these responses may not be exclusively attributable to ER stress and could partially arise from ER stress-independent effects of TM, these findings offer fundamental insights into BA metabolism in response to exogenous chemicals and suggest that ER stress contributes to increased systemic BA circulation when hepatic function is compromised.
Optimum eating ripeness is critical when selecting peaches for consumption; however, the underlying sensory drivers remain unclear. This study identified the sensory factors characterizing the perceived optimum eating ri...Optimum eating ripeness is critical when selecting peaches for consumption; however, the underlying sensory drivers remain unclear. This study identified the sensory factors characterizing the perceived optimum eating ripeness of the melting flesh peach. Seven sample conditions were established from postharvest peaches based on the ripening days, where perceived ripeness shifted from unripe to optimum and then to overripe. The early phase was dominated by sensory textural changes (e.g. "crispiness") and the development of "peach-identity (ID)" flavor, while the late phase was predominated by an increase in "overripe" flavor. Instrumental firmness and ethyl acetate levels changed, accompanied by sensory textures and "overripe" flavor, respectively. These physicochemical indicators distinguished samples in different ripening phases. These findings highlight key sensory and physicochemical indicators for evaluating the optimum eating ripeness in peaches, reflecting the relationship between human perception and fruit biochemical changes and providing a foundation for improved postharvest quality management and consumer satisfaction.
Concise and enantioselective synthesis of highly oxygenated cyclohexanoid natural products (+)-SDEF 678 metabolite and (+)-speciosins A, C, and L was achieved from commercially available d-quinic acid. This synthesis inc...Concise and enantioselective synthesis of highly oxygenated cyclohexanoid natural products (+)-SDEF 678 metabolite and (+)-speciosins A, C, and L was achieved from commercially available d-quinic acid. This synthesis included diastereoselective nucleophilic epoxidation, Sonogashira cross-coupling, and β-elimination as common steps. Their absolute configurations were unambiguously determined by comparing optical rotations between the synthetic and natural products.
Marine ferromanganese (Fe-Mn) oxides serve as both reactive interfaces and long-term archives for oceanography and environmental changes on the Earth. These oxides are ubiquitous in the ocean and provide reactive mineral...Marine ferromanganese (Fe-Mn) oxides serve as both reactive interfaces and long-term archives for oceanography and environmental changes on the Earth. These oxides are ubiquitous in the ocean and provide reactive mineral surfaces that control elemental abundances and isotope ratios in seawater. Recent synchrotron-based spectroscopy and high-precision isotope analyses have significantly improved the molecular-scale understanding of elemental partitioning and isotope fractionation, which establishes a basis for understanding the relationships between minerals and seawater. Hydrogenetic Fe-Mn crusts, which grow extremely slowly on the seafloor, archive paleoceanographic information over tens of millions of years, including ocean chemistry, water mass structure, and ocean circulation. Furthermore, ancient terrestrial Fe-Mn deposits provide constraints on the oxygenation of Earth's surface as a consequence of interactions among the atmosphere, ocean, lithosphere, and biosphere. Progress in Fe-Mn oxide research will facilitate a deeper understanding of ocean chemistry, and the evolution of marine and Earth systems.
Honey bee Apis mellifera L. adults exhibit a sterol composition dominated by phytosterols such as 24-methylene-cholesterol and β-sitosterol, while most insects possess cholesterol as a primary sterol. To examine whether...Honey bee Apis mellifera L. adults exhibit a sterol composition dominated by phytosterols such as 24-methylene-cholesterol and β-sitosterol, while most insects possess cholesterol as a primary sterol. To examine whether sterol composition varies by social roles, we analyzed nurse bees and foragers using gas chromatography-mass spectrometry. The analysis showed the four phytosterols, with 24-methylene-cholesterol being predominant. Honey, a dietary source for honey bees, contained more campesterol than in the whole body, suggesting possible metabolic use. Few significant differences in sterol compositions among tissues indicated that sterol metabolism is not tissue specific. However, social roles influenced different sterol compositions; nurse bees had higher β-sitosterol and isofucosterol, while foragers had more 24-methylene-cholesterol. Additionally, nurse bees retained more 24-methylene-cholesterol in their midgut. These findings suggest that sterol metabolism is influenced by social roles, probably due to differences in diet, absorption, or retention, rather than tissue dependent metabolism.
Tryptanthrin, an ingredient of Persicaria tinctoria, has been reported to exhibit antioxidant and anti-inflammatory effects. To elucidate the potential role of tryptanthrin in periodontal disease, we investigated its eff...Tryptanthrin, an ingredient of Persicaria tinctoria, has been reported to exhibit antioxidant and anti-inflammatory effects. To elucidate the potential role of tryptanthrin in periodontal disease, we investigated its effects on bone metabolism and innate immunity, including the epithelial barrier. RAW264.7 cells were cultured with soluble receptor activator of nuclear factor-κB ligand and tryptanthrin, and stained with tartrate-resistant acid phosphatase to evaluate osteoclastgenesis. The expression of osteoclast differentiation markers was examined using western blot analysis. OBA-9 cells were cultured with tryptanthrin, and the expression of tight junction (TJ) proteins and cell adhesion molecules (CAMs) was examined by western blot analysis. We found that tryptanthrin significantly inhibited osteoclastgenesis and suppressed the expression of osteoclast differentiation markers. Further, tryptanthrin enhanced the expression of TJ proteins and CAMs. These results indicated that tryptanthrin inhibits osteoclastgenesis by downregulating the osteoclast differentiation markers and enhances cell-cell adhesion by upregulating TJ proteins and CAMs.
Toma S, Mizuno G, Yamada H
… +13 more, Munetsuna E, Wakasugi T, Kamiya Y, Nakanishi S, Kagami A, Ishii H, Ando Y, Yamazaki M, Ishikawa H, Suzuki K, Ohashi K, Ohta Y, Okazaki M
Epidemiological and experimental studies have shown that low methylmercury (MeHg) exposure causes cytotoxic effects. As to such cytotoxic effects, we have supposed that not only MeHg itself but also MeHg interacting with...Epidemiological and experimental studies have shown that low methylmercury (MeHg) exposure causes cytotoxic effects. As to such cytotoxic effects, we have supposed that not only MeHg itself but also MeHg interacting with living environmental factors may cause cytotoxic effects. MeHg exposure is known to induce oxidative stress and cell death via ferroptosis in hepatocytes. In this study, we examined whether MeHg exposure followed by palmitic acid (PA) exposure at low non-toxic concentrations cause oxidative stress and cell death in HepG2 cells. In HepG2 cells combinedly exposed to MeHg and PA at low non-toxic concentrations, cell viability and glutathione peroxidase 4 expression levels were significantly decreased, while reactive oxygen species level was significantly increased. Ferrostatin-1 pretreatment suppressed oxidative stress and cell death found in the HepG2 cells. These results indicate that combined exposure to MeHg and PA at low non-toxic concentrations induces oxidative stress associated cell death in HepG2 cells.
Resistance to inhibitors of cholinesterase 8B (RIC8B) functions as a chaperone and guanine nucleotide exchange factor for Gαs/olf. We focused on RIC8B variant 1 (v1), which is abundantly expressed at the mRNA level, and...Resistance to inhibitors of cholinesterase 8B (RIC8B) functions as a chaperone and guanine nucleotide exchange factor for Gαs/olf. We focused on RIC8B variant 1 (v1), which is abundantly expressed at the mRNA level, and variant 4 (v4), which lacks the C-terminal cradle loop helix (CLH) domain. Together with 3 closely related variants (v2, v3, and v10), we evaluated 5 variants for chaperone activity. HEK293T cells were co-expressed with olfactory receptors (ORs), and odorant-induced cAMP production was used as a functional readout. Among the variants tested, only v4 consistently suppressed cAMP responses. AlphaFold3-based complex structure prediction indicated that v1 forms multiple hydrogen bonds with Gαs via its CLH domain, whereas v4 failed to establish these interactions. This suggests that v4 may be unable to stably adopt the proper binding conformation with Gαs, potentially resulting in improperly folded Gαs that exert a dominant-negative effect on OR responses.
Type Ⅱ diabetes and hypertension often coexist, affecting each other. Suppressing dipeptidyl peptidase-4 (DPP-Ⅳ) and angiotensin-I-converting enzyme (ACE) activity is crucial for managing these conditions. Lentinula edod...Type Ⅱ diabetes and hypertension often coexist, affecting each other. Suppressing dipeptidyl peptidase-4 (DPP-Ⅳ) and angiotensin-I-converting enzyme (ACE) activity is crucial for managing these conditions. Lentinula edodes-stem protein, rich in hydrophobic amino acids, has potential for creating DPP-Ⅳ and ACE inhibitory peptides. This study used this protein, combined with databases, to derive peptides that exhibit dual inhibition of DPP-Ⅳ and ACE activity via enzymatic hydrolysis by Bacillus subtilis protease. The most active fraction (F1-2) had IC50 values of 0.0910 mg/mL (DPP-Ⅳ) and 0.0189 mg/mL (ACE). Following the sequencing of fraction F1-2, screening, and solid-phase synthesis, three novel peptides (EW-1, WR-2, and LP-3) exhibiting >60% inhibition of both DPP-Ⅳ and ACE at 1 mg/mL. These peptides showed no significant toxicity to Caco-2 cells, indicating safety. These findings suggest that peptides derived from the stem of Lentinula edodes are promising candidates for health products targeting type Ⅱ diabetes and hypertension.
Peptone is a promising raw material for culturing microorganisms and mammalian cells, but its composition remains unclear. Here, 36 different peptones were comprehensively quantified using five approaches: gas chromatogr...Peptone is a promising raw material for culturing microorganisms and mammalian cells, but its composition remains unclear. Here, 36 different peptones were comprehensively quantified using five approaches: gas chromatography/tandem mass spectrometry, liquid chromatography/mass spectrometry, ion chromatography, postcolumn detection-high-performance liquid chromatography, and inductively coupled plasma mass spectrometry (named multimodal targeting analysis). Seventy-eight chemical compounds/ions were detected among 121 targets, including amino acids, nucleic acids, organic acids, sugars, vitamins, and minerals. The sum of the quantitated component weights exceeded 65% of the total weight in all cases (mean 88%). Principal component and cluster dendrogram analyses revealed clear distinctions between not only peptone brands but also production lots. Plant peptones exhibited greater variety than casein and meat peptones. Partial least squares analysis identified components specific to particular manufacturing processes and peptone sources. Acid-digested peptones contained more free amino acids, including Ala, Cys, Gly, Thr, Ser, Asp, Glu, and Pro, than enzyme-digested types.
Cells must recycle stalled ribosomes while preventing the accumulation of aberrant nascent chains. In bacteria, this is achieved by overlapping pathways with distinct substrates: ribosome-rescue systems act mainly on non...Cells must recycle stalled ribosomes while preventing the accumulation of aberrant nascent chains. In bacteria, this is achieved by overlapping pathways with distinct substrates: ribosome-rescue systems act mainly on non-stop mRNAs, whereas ribosome-associated quality control (RQC) targets mid-ORF arrests. Work in Gram-positive bacteria defined an RQC mechanism that appends C-terminal degrons to stalled peptides, yet the full set of bacterial substrates and splitting factors remains unresolved, and enteric bacteria notably lack a canonical RQC elongation factor. This review traces the field from the discovery of tmRNA (also known as 10Sa RNA or SsrA RNA) through alternative rescue pathways to the current bacterial RQC framework. I summarize mechanisms across three layers-processing of 50S-peptidyl-tRNA, collision sensing and splitting, and downstream proteolysis-and compare species-level strategies and conservation patterns. I highlight how rescue and quality control intersect during phage infection, and outline key mechanistic uncertainties and experiments needed to resolve them.
Thrombopoietin (TPO) is essential for treating thrombocytopenia, but its clinical use is limited by immunogenicity and short half-life. TMP, a TPO mimetic peptide, addresses these issues but requires fusion with carriers...Thrombopoietin (TPO) is essential for treating thrombocytopenia, but its clinical use is limited by immunogenicity and short half-life. TMP, a TPO mimetic peptide, addresses these issues but requires fusion with carriers to improve pharmacokinetics. This study developed ELP-TMP fusion proteins (ELP120-2TMP and 2TMP-ELP120) to extend half-life and enhance activity via elastin-like polypeptide (ELP). Results showed EC50 values of 5.81 n m for ELP120-2TMP and 10.88 n m for 2TMP-ELP120, compared to 2.65 n m for recombinant human TPO (rhTPO). At a dose of 600 nmol/kg, ELP120-2TMP resulted in peak platelet counts in mice on day 20, exhibiting a half-life of 22.9 h. Conversely, 2TMP-ELP120 achieved peak platelet counts on day 12, with a half-life of 25.4 h. The half-lives of both fusion proteins were significantly longer than that reported 2TMP alone (1 h). Area under the curve indicated superior platelet stimulation over rhTPO (P < 0.01).