A self‐wiping co‐rotating twin‐screw extruder (TSE) is operated in a starved state in which the screws are partially filled with resin. Understanding the resin distribution on the screw surface of a ...TSE in this state is essential for the design, operation, and maintenance of the twin‐screw extrusion process. Accordingly, in this study, the circumferential and axial distribution of resin in a TSE were simulated using a novel method combining the mathematical formulation of Hele–Shaw flow, the finite element method, and a newly developed down‐wind pressure updating scheme. The results of the simulation were found to be in good agreement with experimental measurements. The proposed simulation method enables the detailed visualization of resin distribution in the entire axial and circumferential directions over the length of a TSE, improving the ability to determine both the devolatilization and fiber attrition during the extrusion process.
Cholinergic signaling, which modulates cell activities via nicotinic and muscarinic acetylcholine receptors (n- and mAChRs) in response to internal or external stimuli, has been demonstrated in ...mammalian non-neuronal cells that synthesize acetylcholine (ACh). One of the major pathways of excitatory transmission in the enteric nervous system (ENS) is mediated by cholinergic transmission, with the transmitter ACh producing excitatory potentials in postsynaptic effector cells. In addition to ACh-synthesizing and ACh-metabolizing elements in the ENS, the presence of non-neuronal ACh machinery has been reported in epithelial cells of the small and large intestines of rats and humans. However, little is known about how non-neuronal ACh controls physiological function in the intestine. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture suggest that endogenous ACh is synthesized in the intestinal epithelium to drive organoid growth and differentiation through activation of nAChRs. Treatment of organoids with nicotine enhanced cell growth and the expression of marker genes for stem and epithelial cells. On the other hand, the nAChR antagonist mecamylamine strongly inhibited the growth and differentiation of organoids, suggesting the involvement of nAChRs in the regulation of proliferation and differentiation of Lgr5-positive stem cells. More specifically, RNA sequencing analysis revealed that
expression was dramatically upregulated after nicotine treatment, and Wnt5a rescued organoid growth and differentiation in response to mecamylamine. Taken together, our results indicate that coordinated activities of nAChR and Wnt signaling maintain Lgr5-positive stem cell activity and balanced differentiation. Furthermore, we could clearly separate the two groups, neuronal ACh in the ENS and non-neuronal ACh in the intestinal epithelium. Dysfunction of the non-neuronal cholinergic system is involved in the pathogenesis of disease. The data will increase our understanding of the cholinergic properties of non-neuronal cells and lead to optimization of drug therapy.
Plant physiological, epidemiological, and food science studies have shed light on lignans as healthy diets for the reduction of the risk of lifestyle-related noncommunicable diseases and, thus, the ...demand for lignans has been rapidly increasing. However, the low efficiency and instability of lignan production via extraction from plant resources remain to be resolved, indicating the requirement for the development of new procedures for lignan production. The metabolic engineering of lignan-biosynthesizing plants is expected to be most promising for efficient, sustainable, and stable lignan production. This is supported by the recent verification of biosynthetic pathways of major dietary lignans and the exploration of lignan production via metabolic engineering using transiently gene-transfected or transgenic plants. The aim of this review is to present an overview of the biosynthetic pathways, biological activities, and metabolic engineering of lignans and also perspectives in metabolic engineering-based lignan production using transgenic plants for practical application.
Mucin 5AC (MUC5AC) is excessively secreted in the respiratory tract of patients with asthma. Suppressing this secretion is important for improving the air passages, which facilitates easy breathing. ...We have previously reported that the addition of type IV collagen, a typical extracellular matrix (ECM) protein, to the culture medium for human cell lines and primary cells reduced MUC5AC secretion. In this report, we further investigated the effect of type IV collagen on MUC5AC secretion
in vivo
. We employed ovalbumin (OVA)-sensitized mice to model of asthma and exposed them to type IV collagen to verify the reducing effect of MUC5AC
in vivo
. The amount of MUC5AC in bronchoalveolar lavage fluid was examined after nebulization of type IV collagen. Hypersecretion of MUC5AC of the OVA-sensitized mice was suppressed by type IV collagen exposure in a time- and dose-dependent manner. Furthermore, type IV collagen exposure to OVA-sensitized mice decreased integrin α2 and β1 expression in the lungs and increased the levels of Akt and extracellular signal-regulated kinase (ERK) phosphorylation in the trachea. These results suggest that type IV collagen suppresses MUC5AC hypersecretion
via
modulating integrin expression and Akt/ERK phosphorylation in the respiratory tract of the OVA-sensitized mice.
The surface of the human respiratory tract is covered with a mucus layer containing mucin 5AC (MUC5AC) and mucin 5B (MUC5B) as the main components. This layer contributes to biological defense by ...eliminating irritants, but excessive MUC5AC secretion by the airway epithelial cells exacerbates asthma. Therefore, regulating mucin production is important for asthma treatment. In this study, the effects of integrin β1 subunit on MUC5AC and MUC5B production were examined in NCI–H292 human lung cancer epithelial cells. When integrin β1 was overexpressed, cellular and secreted MUC5AC levels were decreased, whereas cellular MUC5B production was increased. Conversely, integrin β1 depletion using siRNA increased cellular and secreted MUC5AC production, but decreased cellular MUC5B production. Further, the activity of extracellular signal-regulated kinase (ERK), which promotes MUC5AC production, was decreased by integrin β1 overexpression and increased by its depletion. These results suggest that integrin β1 suppresses MUC5AC production and promotes MUC5B production by downregulating ERK.
•We studied the regulation of MUC5AC and MUC5B production by integrin β1 subunit.•Integrin β1 overexpression reduced MUC5AC, but increased MUC5B levels.•Integrin β1 depletion increased MUC5AC production and ROS level, but decreased MUC5B production.•Integrin β1 overexpression decreased ERK activity in NCI–H292 airway cells.•Integrin β1 downregulates ERK to suppress MUC5AC & promote MUC5B production.
The present study aimed to evaluate the quantitative and qualitative effectiveness of an undergraduate course entitled, 'What is disability?' Specifically, we measured changes in perceptions of ...Japanese freshmen towards people with disabilities (PWDs) using the Disability Social Work scale, and what they learned from the course. In total, 18 freshmen university students (8 females, 10 males; mean age, 18.5 years; age range, 18 to 21 years) collectively majoring in literature, education, medicine, law, economics, engineering, and pharmacology registered for the course. Pre- and post-tests showed significant improvements in the participants' perceptions of disability rejection, psychological distance from disability, and the idea that PWDs are incapable of managing tasks. A qualitative analysis yielded two conceptual categories, changed perceptions towards disability and PWDs and gaining new perspectives on disability and PWDs. The first category consists of three subcategories (trivialising disability, increasing psychological proximity towards disability, and 'do PWDs really want our support?') and the second category consists of two subcategories (recognising dichotomy of difficulty and capability in disability and recognising his/her own ableism).
This study examined the validity of a practical evaluation method for pitting edema by comparing it to other methods, including circumference measurements and ultrasound image measurements. Fifty-one ...patients (102 legs) from a convalescent ward in Maruyama Hospital were recruited for study 1, and 47 patients (94 legs) from a convalescent ward in Morinaga Hospital were recruited for study 2. The relationship between the depth of the surface imprint and circumferential measurements, as well as the relationship between the depth of the surface imprint and the thickness of the subcutaneous soft tissue on an ultrasonogram, were analyzed using a Spearman correlation coefficient by rank. There was no significant relationship between the surface imprint depth and circumferential measurements. However, there was a significant relationship between the depth of the surface imprint and the thickness of the subcutaneous soft tissue as measured on an ultrasonogram (correlation coefficient 0.736). Our findings suggest that our novel evaluation method for pitting edema, based on a measurement of the surface imprint depth, is both valid and useful.
Summary
Sesame (Sesamum indicum) seeds contain a large number of lignans, phenylpropanoid‐related plant specialized metabolites. (+)‐Sesamin and (+)‐sesamolin are major hydrophobic lignans, whereas ...(+)‐sesaminol primarily accumulates as a water‐soluble sesaminol triglucoside (STG) with a sugar chain branched via β1→2 and β1→6‐O‐glucosidic linkages i.e. (+)‐sesaminol 2‐O‐β‐d‐glucosyl‐(1→2)‐O‐β‐d‐glucoside‐(1→6)‐O‐β‐d‐glucoside. We previously reported that the 2‐O‐glucosylation of (+)‐sesaminol aglycon and β1→6‐O‐glucosylation of (+)‐sesaminol 2‐O‐β‐d‐glucoside (SMG) are mediated by UDP‐sugar‐dependent glucosyltransferases (UGT), UGT71A9 and UGT94D1, respectively. Here we identified a distinct UGT, UGT94AG1, that specifically catalyzes the β1→2‐O‐glucosylation of SMG and (+)‐sesaminol 2‐O‐β‐d‐glucosyl‐(1→6)‐O‐β‐d‐glucoside termed SDG(β1→6). UGT94AG1 was phylogenetically related to glycoside‐specific glycosyltransferases (GGTs) and co‐ordinately expressed with UGT71A9 and UGT94D1 in the seeds. The role of UGT94AG1 in STG biosynthesis was further confirmed by identification of a STG‐deficient sesame mutant that predominantly accumulates SDG(β1→6) due to a destructive insertion in the coding sequence of UGT94AG1. We also identified UGT94AA2 as an alternative UGT potentially involved in sugar–sugar β1→6‐O‐glucosylation, in addition to UGT94D1, during STG biosynthesis. Yeast two‐hybrid assays showed that UGT71A9, UGT94AG1, and UGT94AA2 were found to interact with a membrane‐associated P450 enzyme, CYP81Q1 (piperitol/sesamin synthase), suggesting that these UGTs are components of a membrane‐bound metabolon for STG biosynthesis. A comparison of kinetic parameters of these UGTs further suggested that the main β‐O‐glucosylation sequence of STG biosynthesis is β1→2‐O‐glucosylation of SMG by UGT94AG1 followed by UGT94AA2‐mediated β1→6‐O‐glucosylation. These findings together establish the complete biosynthetic pathway of STG and shed light on the evolvability of regio‐selectivity of sequential glucosylations catalyzed by GGTs.
Significance Statement
Sesaminol triglucoside (STG) of sesame seeds has unique bioactivities with potential health benefits, yet the STG biosynthesis pathway remains to be fully established. This study has identified the missing enzyme in STG biosynthesis that catalyzes β1→2‐O‐glucosylation, a regioselective sequential glycosylation of sesame lignan biosynthesis.
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