In the previous paper, it was elucidated that several conditionings such as frozen storage of mixed dough and adding a small amount of egg lecithin had improved the bread baking properties of soy 11S ...globulin, however, the same conditionings had effected oppositely in soy 7S globulin. Therefore, the enlargement of molecular size of 7S globulin through reacting with epichlorohydrin was tried and the product, modified 7S globulin, showed the excellent bread baking properties when added a small amount of egg lecithin. These properties of modified 7S globulin resembled significantly to soy 11S globulin. Therefore, the changes of bread baking properties of modified 7S globulin as affected by combining with soy 11S globulin were examined. The combination of original 7S and 11S globulins gave the inferior breads, respectively. Oppositely, the combination of modified 7S and 11S globulins gave the excellent breads by adding of 0. 1% egg lecithin. These differences between original and modified 7S globulin were tried to clarify through determining the differences of Formol titration value in their trypsin proteolysates as described previously. However, the clear results to show such differences in both globulins were not obtained.
Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases (HAS) at the plasma membrane and comprises the backbone of perineuronal nets around neuronal soma and dendrites. However, the ...molecular targets of hyaluronan to regulate synaptic transmission in the central nervous system have not been fully identified. Here, we report that hyaluronan is a negative regulator of excitatory signals. At excitatory synapses, glutamate is removed by glutamate transporters to turn off the signal and prevent excitotoxicity. Hyaluronan synthesized by HAS supports the activity of glial glutamate transporter 1 (GLT1). GLT1 also retracted from cellular processes of cultured astrocytes after hyaluronidase treatment and hyaluronan synthesis inhibition. A serial knockout study showed that all three HAS subtypes recruit GLT1 to cellular processes. Furthermore, hyaluronidase treatment activated neurons in a dissociated rat hippocampal culture and caused neuronal damage due to excitotoxicity. Our findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance.
Cover Image for this issue: doi: 10.1111/jnc.14516.
At excitatory synapses, glutamate is removed by glutamate transporters to turn off the signal. Hyaluronan is synthesized, secreted, and anchored by hyaluronan synthases at the plasma membrane. We show that hyaluronan is synthesized to support glutamate uptake by glutamate transporters. Hyaluronan synthases and glutamate transporters form a hyaluronan dependent complex, and are recruited to cellular process tips. These findings reveal that hyaluronan helps to turn off excitatory signals by supporting glutamate clearance for healthy excitatory signal tuning.
Cover Image for this issue: doi: 10.1111/jnc.14516.
Molecular mechanisms for the establishment of transcriptional memory are poorly understood. 5,6-dichloro-1-D-ribofuranosyl-benzimidazole (DRB) is a P-TEFb kinase inhibitor that artificially induces ...the poised RNA polymerase II (RNAPII), thereby manifesting intermediate steps for the establishment of transcriptional activation. Here, using genetics and DRB, we show that mammalian Absent, small, or homeotic discs 1-like (Ash1l), a member of the trithorax group proteins, methylates Lys36 of histone H3 to promote the establishment of Hox gene expression by counteracting Polycomb silencing. Importantly, we found that Ash1l-dependent Lys36 di-, tri-methylation of histone H3 in a coding region and exclusion of Polycomb group proteins occur independently of transcriptional elongation in embryonic stem (ES) cells, although both were previously thought to be consequences of transcription. Genome-wide analyses of histone H3 Lys36 methylation under DRB treatment have suggested that binding of the retinoic acid receptor (RAR) to a certain genomic region promotes trimethylation in the RAR-associated gene independent of its ongoing transcription. Moreover, DRB treatment unveils a parallel response between Lys36 methylation of histone H3 and occupancy of either Tip60 or Mof in a region-dependent manner. We also found that Brg1 is another key player involved in the response. Our results uncover a novel regulatory cascade orchestrated by Ash1l with RAR and provide insights into mechanisms underlying the establishment of the transcriptional activation that counteracts Polycomb silencing.
This study provided a rough estimate incidence of primary pediatric central diabetes insipidus (CDI) and examines the diagnostic factors between pediatric CDI and primary polydipsia (PP).
We ...collected 27 patients with chief complaints of polyuria and/or polydipsia from January 2014 to December 2018 in the Department of Pediatrics, Our University Hospital.
We diagnosed type 1 diabetes mellitus (T1DM) in 16 patients, CDI in 5, PP in 5, and nocturnal enuresis in 1. The rough estimate incidence rate of pediatric CDI was 0.71/100,000/year. The diagnostic factors were a body mass index (BMI), urine gravity in the morning, urine volume and intake volume over 24 h, and bright spots in the posterior pituitary in a magnetic resonance image (MRI). The cutoff value of urine gravity in the morning for CDI was <1.010, with a sensitivity of 100 % and specificity of 100 %. The cutoff value of urine volume over 24 h for CDI was >2299 mL/m2, with a sensitivity of 100 % and specificity of 85.7 %. No pediatric CDI patients had the bright spot in the posterior pituitary of their MRI, using a type 1–weighted image; however, only 1 out of 4 PP patients did not show the bright spot.
The rough estimate incidence of pediatric CDI with polydipsia and polyuria under the limited condition was 0.71/100,000/year, which was very low. Distinguishable factors between CDI patients and PP patients were BMI, urine and intake volumes over 24 h, and a bright spot on an MRI. Further studies with multiple institutes and more patients are required to confirm these findings.
•The rough estimate incidence rate of pediatric central diabetes insipidus was 0.71/100,000/year.•The diagnostic factors were a BMI, urine gravity in the morning, urine/intake volume per day, and bright spots in the posterior pituitary on MRI.•The cutoff value of urine gravity in the morning and urine volume for CDI was <1.010, and >2,299 mL/m2, respectively.
Rheumatoid arthritis (RA) is a chronic inflammatory articular disease that is characterized by synovial hyperplasia. A number of signaling pathways are associated with the development and induced ...symptoms of RA. Notably, patients with RA have increased protein citrullination and generation of auto‑antibodies against citrullinated proteins. Genome wide association studies have revealed that peptidyl‑arginine deiminase 4 (PADI4) is an enzyme implicated in citrullination in the RA synovium. Autoantibodies targeting citrullinated proteins are used as diagnostic markers in patients with RA. The functions associated with citrullinated proteins are thought to induce autoimmunity, however, the regulatory mechanisms of citrullination via PADI4 are unclear. The group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the RA synovium, demonstrating that SYVN1 serves critical roles in synovial hyperplasia. The data indicated that the endoplasmic reticulum (ER) associated degradation system, which involves SYVN1, may have important roles in the proliferation of synoviocytes. In addition, ubiquitination by SYVN1 is associated with fibrosis, inflammation and cytokine production via the regulation of ER stress signals and quality control of proteins. The present study investigated the crosstalk between the representative post‑translational signaling processes, citrullination and ubiquitination. The results revealed that PADI4 interacted with SYVN1 directly and that overexpression of PADI4 suppressed the ubiquitination of proteins. Thus, a reduction in ER stress induced by PADI4 may abrogate the initiation of chronic RA by suppressing the proliferative signals of RA synoviocytes.
Information about mechanical reinforcement of decorative organs could help development of a novel technique that would give flowers with robust floral organs and broadly contribute to postharvest ...flower preservation. Hydrangeas (Hydrangea spp.) exhibit remarkable characteristics in terms of mechanical reinforcement of decorative sepals. Although decorative sepals at the flowering stage shrink when they are desiccated, decorative sepals after flowering maintain their shape even after desiccation. In this study, the lignifications of the vein cells in decorative sepals were analyzed using phloroglucinol/HCl-staining. The microstructure of the cell wall was analyzed using transmission electron microscopy (TEM). The three-dimensional structure of vein cells was analyzed using serial block-face scanning electron microscopy (SBF-SEM). Tubular- and spindle-shaped dead cells with a lignified pitted secondary cell wall were observed around the vessel elements in decorative sepals after flowering. These cells were observed as living cells without a secondary cell wall in the veins of decorative sepals at flowering and in fully expanded leaves. Further, 10 hydrangea cultivars were analyzed for development of mechanical reinforcement in vein cells, and some of them were compared by desiccation testing. Decorative sepals of a cultivar lacking those cells exhibited shrinkage after flowering when they were desiccated. In conclusion, dead cells with a lignified pitted secondary cell wall contribute to the reinforcement of veins in decorative sepals of hydrangeas and become sclerified parenchyma cells. Axial parenchyma sclerifying in veins after flowering is essential for robust hydrangea floral organs and represent a new type of mechanical reinforcement tissue in plant decorative floral organs.
The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza virus infection in Japan in February 2018. Two influenza A(H3N2) viruses carrying an I38T ...substitution in the polymerase acidic subunit (PA) were detected in baloxavir-treated children in December 2018. This mutation is known to confer reduced susceptibility to baloxavir, and the two mutant viruses exhibited 76- and 120-fold reduced susceptibility to baloxavir.
To assess the efficacy and safety of branched chain amino acids (BCAAs) in the treatment of PM/DM prior to official approval of their use in Japan.
Treatment naïve adults with PM/DM were enrolled in ...a randomized, double-blind trial to receive either TK-98 (drug name of BCAAs) or placebo in addition to conventional treatment. After 12 weeks, patients with an average manual muscle test (MMT) score <9.5 were enrolled in an open label extension study for a further 12 weeks. The primary endpoint was the change of the MMT score at 12 weeks. The secondary endpoints were the clinical response and the change of functional index (FI).
Forty-seven patients were randomized either to the TK-98 (n = 24) or placebo (n = 23) group. The changes of MMT scores at 12 weeks were 0.70 (0.19) mean (s.e.m.) and 0.69 (0.18), respectively (P = 0.98). Thirteen patients from the TK-98 group and 12 from the placebo group were enrolled in the extension study. The MMT scores in both groups improved similarly. The increase of the FI scores of the shoulder flexion at 12 weeks was significantly greater in the TK-98 group 27.9 (5.67) vs 12.8 (5.67) for the right shoulder flexion, and 27.0 (5.44) vs 13.4 (5.95) for the left shoulder; P < 0.05. Frequencies of adverse events up to 12 weeks were similar.
BCAAs showed no effect on the improvement of the muscle strength evaluated by MMT and the clinical response. However, they were partly effective for improving dynamic repetitive muscle functions.
UMIN-CTR Clinical Trial, https://center6.umin.ac.jp/, UMIN000016233.
PDF
