A fully human neutralizing monoclonal antibody targeting a highly conserved epitope of the human cytomegalovirus glycoprotein B.

Human cytomegalovirus causes severe diseases in children (by congenital infection) and immunocompromised patients. Treatment with antiviral agents, such as ganciclovir, is limited by their toxicity. In this study, we investigated the effectiveness of a fully human neutralizing monoclonal antibody to inhibit human cytomegalovirus infection and viral cell-to-cell spread. We isolated a potent neutralizing antibody, EV2038 (IgG1 lambda), targeting human cytomegalovirus glycoprotein B using Epstein-Barr virus transformation. This antibody inhibited human cytomegalovirus infection by all four laboratory strains and 42 Japanese clinical isolates, including ganciclovir-resistant isolates, with a 50% inhibitory concentration (IC50) ranging from 0.013 to 0.105 μg/mL, and 90% inhibitory concentration (IC90) ranging from 0.208 to 1.026 μg/mL, in both human embryonic lung fibroblasts (MRC-5) and human retinal pigment epithelial (ARPE-19) cells. Additionally, EV2038 prevented cell-to-cell spread of eight clinical viral isolates, with IC50 values ranging from 1.0 to 3.1 μg/mL, and IC90 values ranging from 13 to 19 μg/mL, in ARPE-19 cells. EV2038 recognized three discontinuous sequences on antigenic domain 1 of glycoprotein B (amino acids 549-560, 569-576, and 625-632), which were highly conserved among 71 clinical isolates from Japan and the United States. Pharmacokinetics study in cynomolgus monkeys suggested the potential efficacy of EV2038 in vivo, the concentration of which in serum remained higher than the IC90 values of cell-to-cell spread until 28 days after intravenous injection of 10 mg/kg EV2038. Our data strongly support EV2038 as a promising candidate and novel alternative for the treatment of human cytomegalovirus infection

Neural effects of acute stress on appetite: A magnetoencephalography study.

Stress is prevalent in modern society and can affect human health through its effects on appetite. Therefore, in the present study, we aimed to clarify the neural mechanisms by which acute stress affects appetite in healthy, non-obese males during fasting. In total, 22 volunteers participated in two experiments (stress and control conditions) on different days. The participants performed a stress-inducing speech-and-mental-arithmetic task under both conditions, and then viewed images of food, during which, their neural activity was recorded using magnetoencephalography (MEG). In the stress condition, the participants were told to perform the speech-and-mental-arithmetic task again subsequently to viewing the food images; however, another speech-and-mental-arithmetic task was not performed actually. Subjective levels of stress and appetite were then assessed using a visual analog scale. Electrocardiography was performed to assess the index of heart rate variability reflecting sympathetic nerve activity. The findings showed that subjective levels of stress and sympathetic nerve activity were increased in the MEG session in the stress condition, whereas appetite gradually increased in the MEG session only in the control condition. The decrease in alpha band power in the frontal pole caused by viewing the food images was greater in the stress condition than in the control condition. These findings suggest that acute stress can suppress the increase of appetite, and this suppression is associated with the frontal pole. The results of the present study may provide valuable clues to gain a further understanding of the neural mechanisms by which acute stress affects appetite. However, since the stress examined in the present study was related to the expectation of forthcoming stressful event, our present findings may not be generalized to the stress unrelated to the expectation of forthcoming stressful event

De Novo Accumulation of Tetrodotoxin and Its Analogs in Pufferfish and Newt and Dosage-Driven Accumulation of Toxins in Newt: Tissue Distribution and Anatomical Localization

The present study was undertaken to determine the amounts of tetrodotoxin (TTX) and its analogs (TTXs) in various tissues of toxin-bearing pufferfish (Canthigaster revulata and Takifugu flavipterus) and newt (Cynops pyrrhogaster) using specific polyclonal antibodies against TTXs, and to compare the obtained results with those mainly determined by high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The anatomical localization of TTXs in these animals was also demonstrated immunohistochemically using the above-mentioned antibody. The ratio of the total amount of TTXs determined by ELISA to that determined by HPLC-FLD changed depending on the tissues examined in pufferfish. Such differences were also observed with the newt in tissue- and individual-dependent manners. Furthermore, TTXs, as well as decarbamoylsaxitoxin (dcSTX), an analog of saxitoxin (STX), were traced for their dynamic changes in tissue distribution, when the newt was fed authentic toxins or toxic animal tissues exogenously, demonstrating that a TTX analog, 5,6,11-trideoxyTTX, and dcSTX were not metabolized into TTX or STX. TTXs-immunoreactive (ir) staining was observed in the pancreas region of the hepatopancreas, the oocytes at the perinucleolus stage, the sac-like tissues just outside the serous membrane of the intestine, and the gland-like structure of the skin, but not in the muscles of pufferfish. TTXs-ir staining was also detected in the mature glands in the dermis of the adult and regenerated tail, but not in the liver, intestine, testis and ovary of the adult newt. TTXs-ir staining was detected in the epithelial cells of the intestine, the ovary, the mucous cells, and the dermis of the TTXs-administered newt. These results suggest that TTXs absorbed from the environment are distributed to various organs or tissues in a species-specific manner, regardless of whether or not these are metabolized in the bodies of toxin-bearing animals

Anion-Controlled Assembly of Four Manganese Ions: Structural, Magnetic, and Electrochemical Properties of Tetramanganese Complexes Stabilized by Xanthene-Bridged Schiff Base Ligands

The reaction of manganese­(II) acetate with a xanthene-bridged bis­[3-(salicylideneamino)-1-propanol] ligand, H₄L, afforded the tetramanganese­(II,II,III,III) complex [Mn₄(L)₂(μ-OAc)₂], which has an incomplete double-cubane structure. The corresponding reaction using manganese­(II) chloride in the presence of a base gave the tetramanganese­(III,III,III,III) complex [Mn₄(L)₂Cl₃(μ₄-Cl)­(OH₂)], in which four Mn ions are bridged by a Cl^– ion. A pair of L ligands has a propensity to incorporate four Mn ions, the arrangement and oxidation states of which are dependent on the coexistent anions

Anion-Controlled Assembly of Four Manganese Ions: Structural, Magnetic, and Electrochemical Properties of Tetramanganese Complexes Stabilized by Xanthene-Bridged Schiff Base Ligands

The reaction of manganese­(II) acetate with a xanthene-bridged bis­[3-(salicylideneamino)-1-propanol] ligand, H₄L, afforded the tetramanganese­(II,II,III,III) complex [Mn₄(L)₂(μ-OAc)₂], which has an incomplete double-cubane structure. The corresponding reaction using manganese­(II) chloride in the presence of a base gave the tetramanganese­(III,III,III,III) complex [Mn₄(L)₂Cl₃(μ₄-Cl)­(OH₂)], in which four Mn ions are bridged by a Cl^– ion. A pair of L ligands has a propensity to incorporate four Mn ions, the arrangement and oxidation states of which are dependent on the coexistent anions

Foodborne Outbreaks Caused by Human Norovirus GII.P17-GII.17–Contaminated Nori, Japan, 2017

Seven foodborne norovirus outbreaks attributable to the GII.P17-GII.17 strain were reported across Japan in 2017, causing illness in a total of 2,094 persons. Nori (dried shredded seaweed) was implicated in all outbreaks and tested positive for norovirus. Our data highlight the stability of norovirus in dehydrated food products