Differential effects of brefeldin A on sialylation of N- and O-linked oligosaccharides in low density lipoprotein receptor and epidermal growth factor receptor

Low density lipoprotein receptor (LDL-R) is a membrane glycoprotein carrying both N- and O-linked oligosaccharides, processing of which is reflected in conversion from a precursor to mature form during its synthesis and intracellular transport. Treatment with brefeldin A (BFA) of mouse macrophage-like J774 cells, Chinese hamster ovary cells, and two human cancer cell lines (A431 and IMC-2) resulted in production of LDL-R with a molecular size 5-10 kDa smaller than that of the mature form in the control cells. Treatment with sialidase caused apparent reduction in the molecular size of LDL-R synthesized in all BFA-treated J774, Chinese hamster ovary, A431, and IMC-2 cell lines as observed for the mature form of the control cells. Thus, O-linked sugar chains of LDL-R were apparently sialylated in the BFA-treated cells. We also examined the effect of BFA on the processing of another membranous glycoprotein, epidermal growth factor receptor (EGF-R) carrying only N-linked oligosaccharides. EGF-R synthesized in the presence of BFA was found to have no response to sialidase treatment, suggesting that the drug blocks the sialylation of EGF-R. The results indicate that BFA causes different effects on the sialylation of LDL-R and EGF-R depending upon linkage types of their oligosaccharides.     

Developmental Changes in the Bombyxin-and Insulin-like Immunoreactive Neurosecretory System in the Wax Moth, Galleria mellonella

Four medial neurosecretory cells (MNC) and 4 lateral neurosecretory cells (LNC) in each brain hemisphere, and one pair of cells in each thoracic ganglion (TG) of Galleria larva react with antibodies against bombyxin and insulin. Material secreted from the MNC and LNC is released mainly in the corpora allata, and that from the TG through the ventral median nerves. Intrinsic secretory cells of the corpora cardiaca (CC) also contain bombyxin-like, but not insulin-like material. The immunoreactivities all disappear during molts and reappear with resumption of feeding. In the MNC and TG they reappear for less than a day, but in cells of the CC immunoreactivity reappears for the whole feeding period. Before pupation, the LNC become temporarily immunopositive towards the end of feeding period, and the MNC and TG during the wandering period, i.e. at the time of prothoracic gland stimulation. Immunoreactivity disappears during the pupal molt. In pupae it is present in the 4 pairs of MNC and 1–2 pairs of LNC 12–48 hr after ecdysis, and in cells of the CC from 12 hr after ecdysis until the end of the pupal instar. In adult, immunoreactivity is restricted to 2 pairs of the LNC and to CC cells.     

Seasonal and areal features of the lagoonal environment in Lake Nakanoumi,a shallow coastal lagoon in Japan

Lake Nakanoumi is a shallow coastal lagoon connected with the Japan Sea by a narrow channel. Over the past decade, land reclamation resulted in a 33% reduction of the lagoon's surface area. The remaining water basin of Lake Nakanoumi is scheduled to be artificially freshened to supply irrigation water for the newly reclaimed lands. This paper deals with the seasonal and areal features of the lagoonal environment prior to the beginning of the artificial desalinization.     

Sulfonamide-based non-alkyne LpxC inhibitors as Gram-negative antibacterial agents

We attempted to optimize sulfonamide-based non-alkyne LpxC inhibitors by focusing on improvements in enzyme inhibitory and antibacterial activity. It was discovered that inhibitors possessing 2-aryl benzofuran as a hydrophobe exhibited good activity. In particular, compound 21 displayed impressive antibacterial activity (E. coli MIC = 0.063 μg/mL, K. pneumoniae MIC = 0.5 μg/mL, and P. aeruginosa MIC = 0.5 μg/mL), and is a promising lead for further exploration as an antibacterial agent.     

Studies on the Foaming Property of the Chicken Egg White

The egg white was treated under various whipping conditions, and its foaminess measured. At the same time, the amounts of the coagulated proteins formed from each egg white and their constituent hexose were measured. From these results, discussions were made about the relation between the foaminess of the egg white and the amount of the coagulated proteins under various whipping conditions.     

Mechanism of silicate elution by hydrogen sulfide from bottom sediment in a brackish lake

Limnology - Highly concentrated dissolved silicate was detected in pore water from anoxic-reducing sediment in Lake Nakaumi, a brackish lake. Silicate concentration also simultaneously increased...     

High-dose zolpidem abuse in a patient with insomnia comorbid with major depressive disorder

Sleep and Biological Rhythms - A 39-year-old married woman was referred to a psychiatry outpatient clinic for treatment of major depressive disorder (MDD). The dose of zolpidem she had been taking...     

Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma

Immune checkpoint inhibitors improved the survival rate of patients with unresectable melanoma. However, some patients do not respond, and variable immune‐related adverse events have been reported. Therefore, more effective and antigen‐specific immune therapies are urgently needed. We previously reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS‐ML). In this study, we generated OX40L‐overexpressing iPS‐ML (iPS‐ML‐Zsgreen‐OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS‐ML‐Zsgreen‐OX40L suppressed the progression of B16‐BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)‐expressing B16 melanoma (MO4). The number of antigen‐specific CD8⁺ T cells was higher in spleen cells treated with OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L than in those without OX40L. The OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L significantly increased the number of tumor‐infiltrating T lymphocytes (TILs) in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector and effector memory T cells among the TILs. Although we plan to use allogeneic iPS‐ML in the clinical applications, iPS‐ML showed the tumorgenicity in the syngeneic mice model. Incorporating the suicide gene is necessary to ensure the safety in the future study. Collectively, these results indicate that iPS‐ML‐Zsgreen‐OX40L therapy might be a new method for antigen‐specific cancer immunotherapy.