Reproductive ecology of dominant dinoflagellate, Ceratium furca, in the coastal area of Sagami Bay

Reproductive ecology of dinoflagellate, Ceratium furca, was studied in the coastal area of Sagami Bay. Field samplings and laboratory experiments were conducted to investigate seasonal changes of the field population and effects of temperature, salinity and irradiance on the growth rate of C. furca. Abundance of the species increased significantly from April to September and was decreased in November. In particular, the population increased during the spring when the water column was weakly stratified and relatively low nutrient conditions were observed in the surface layer. High growth rates of C. furca were observed at the conditions of 20-28℃, 17-34 PSU and 216-800μEm^s^ with the highest growth rate (μ=0.72d^) being observed at 24℃, 30 PSU and 600μEm^s^. In addition, the growth rates increased gradually with increasing irradiance from 58 to 216μEm^s^ in the all salinity conditions, and afterwards the rates reached plateaus between 216 and 796μEm^s^. The field survey and laboratory experiments indicated that the species is distributed throughout the year and adapted to a wide-range of environmental fluctuations such as water temperature, salinity, irradiance and nutrients. These specific characteristics make C. furca one of the dominant dinoflagellates in the coastal area

Reproductive strategy of Acartia steueri in Sagami Bay, Japan

Reproduction, hatching success and population dynamics of the dominant copepod Acartia steueri were studied in Sagami Bay, Japan from February 2002 to December 2003. A. steueri occurred through the year in the water column, and it produced physiologically different eggs, subitaneous and diapausing. Subitaneous eggs were produced through the experimental period, whereas diapausing ones were restricted from February to August in both years. Population egg production rate (EPR) increased with the abundance of adult males and females from February and reached maximum in June. However, planktonic population of A. steueri did not increase during summer to winter because diapausing eggs occupied a great part of their reproduction (～98%). Recruitment rates in October to December 2002 and September 2003 were higher than population EPR, implying that diapausing eggs of A. steueri had a key role to support the recruitment into water column when the reproductive ability of the population diminished rather than to contribute to an increase of the planktonic population rapidly in their favorable seasons

Formation of ZnO thin films by photocatalytic reaction

Zinc oxide and layered zinc hydroxides were deposited from an aqueous solution of zinc nitrate at 323–358 K on a substrate plate with a very thin titanium dioxide film by a photocatalytic reaction. The amorphous or low crystalline zinc hydroxide aggregates were deposited at a low temperature. The zinc oxide crystals with about 1–2 μm-sized hexagonal columns and 10 nm-sized spheres were formed at 338–358 K. Nitrate ions in the solution were reduced to nitrite ions, and water was transformed into hydroxide ions by a photocatalytic reaction on the titanium dioxide film. The pH value increased on the substrate surface with the titanium dioxide film, which caused the zinc hydroxide formation on the film. The zinc hydroxides were then dehydrated and transformed into zinc oxide. The average crystallite size of the zinc oxide decreased with an increase in the reaction temperature because the reaction rates of the formation and dehydration of the zinc hydroxides increased which resulted in an increase in the formation rate of the crystal zinc oxide nuclei.ArticleAPPLIED CATALYSIS B-ENVIRONMENTAL. 160:651-657 (2014)journal articl

Switching and Emergence of CTL Epitopes in HIV-1 Infection

Background Human Leukocyte Antigen (HLA) class I restricted Cytotoxic T Lymphocytes (CTLs) exert substantial evolutionary pressure on HIV-1, as evidenced by the reproducible selection of HLA-restricted immune escape mutations in the viral genome. An escape mutation from tyrosine to phenylalanine at the 135th amino acid (Y135F) of the HIV-1 nef gene is frequently observed in patients with HLA-A*24:02, an HLA Class I allele expressed in ~70% of Japanese persons. The selection of CTL escape mutations could theoretically result in the de novo creation of novel epitopes, however, the extent to which such dynamic “CTL epitope switching” occurs in HIV-1 remains incompletely known. Results Two overlapping epitopes in HIV-1 nef, Nef126-10 and Nef134-10, elicit the most frequent CTL responses restricted by HLA-A*24:02. Thirty-five of 46 (76%) HLA-A*24:02-positive patients harbored the Y135F mutation in their plasma HIV-1 RNA. Nef codon 135 plays a crucial role in both epitopes, as it represents the C-terminal anchor for Nef126-10 and the N-terminal anchor for Nef134-10. While the majority of patients with 135F exhibited CTL responses to Nef126-10, none harboring the “wild-type” (global HIV-1 subtype B consensus) Y135 did so, suggesting that Nef126-10 is not efficiently presented in persons harboring Y135. Consistent with this, peptide binding and limiting dilution experiments confirmed F, but not Y, as a suitable C-terminal anchor for HLA-A*24:02. Moreover, experiments utilizing antigen specific CTL clones to recognize endogenously-expressed peptides with or without Y135F indicated that this mutation disrupted the antigen expression of Nef134-10. Critically, the selection of Y135F also launched the expression of Nef126-10, indicating that the latter epitope is created as a result of escape within the former. Conclusions Our data represent the first example of the de novo creation of a novel overlapping CTL epitope as a direct result of HLA-driven immune escape in a neighboring epitope. The robust targeting of Nef126-10 following transmission (or in vivo selection) of HIV-1 containing Y135F may explain in part the previously reported stable plasma viral loads over time in the Japanese population, despite the high prevalence of both HLA-A*24:02 and Nef-Y135F in circulating HIV-1 sequences

Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in 40–69-years subjects

[Background] Visceral fat obesity can be defined quantitatively by abdominal computed tomography, however, the usefulness of measuring visceral fat area to assess the etiology of gastrointestinal reflux disease has not been fully elucidated. [Methods] A total of 433 healthy subjects aged 40–69 years (234 men, 199 women) were included in the study. The relationship between obesity-related factors (total fat area, visceral fat area, subcutaneous fat area, waist circumference, and body mass index) and the incidence of reflux erosive esophagitis was investigated. Lifestyle factors and stomach conditions relevant to the onset of erosive esophagitis were also analyzed. [Results] The prevalence of reflux erosive esophagitis was 27.2% (118/433; 106 men, 12 women). Visceral fat area was higher in subjects with erosive esophagitis than in those without (116.6 cm2 vs. 64.9 cm2, respectively). The incidence of erosive esophagitis was higher in subjects with visceral fat obesity (visceral fat area ≥ 100 cm2) than in those without (61.2% vs. 12.8%, respectively). Visceral fat obesity had the highest odds ratio (OR) among obesity-related factors. Multivariate analysis showed that visceral fat area was associated with the incidence of erosive esophagitis (OR = 2.18), indicating that it is an independent risk factor for erosive esophagitis. In addition, daily alcohol intake (OR = 1.54), gastric atrophy open type (OR = 0.29), and never-smoking history (OR = 0.49) were also independently associated with the development of erosive esophagitis. [Conclusions] Visceral fat obesity is the key risk factor for the development of reflux erosive esophagitis in subjects aged 40–69 years

Formation of ZnO thin films by photocatalytic reaction

Zinc oxide and layered zinc hydroxides were deposited from an aqueous solution of zinc nitrate at 323–358 K on a substrate plate with a very thin titanium dioxide film by a photocatalytic reaction. The amorphous or low crystalline zinc hydroxide aggregates were deposited at a low temperature. The zinc oxide crystals with about 1–2 μm-sized hexagonal columns and 10 nm-sized spheres were formed at 338–358 K. Nitrate ions in the solution were reduced to nitrite ions, and water was transformed into hydroxide ions by a photocatalytic reaction on the titanium dioxide film. The pH value increased on the substrate surface with the titanium dioxide film, which caused the zinc hydroxide formation on the film. The zinc hydroxides were then dehydrated and transformed into zinc oxide. The average crystallite size of the zinc oxide decreased with an increase in the reaction temperature because the reaction rates of the formation and dehydration of the zinc hydroxides increased which resulted in an increase in the formation rate of the crystal zinc oxide nuclei.ArticleAPPLIED CATALYSIS B-ENVIRONMENTAL. 160:651-657 (2014)journal articl

Genetic and chemical inhibition of IRF5 suppresses pre-existing mouse lupus-like disease

The transcription factor IRF5 has been implicated as a therapeutic target for the autoimmune disease systemic lupus erythematosus (SLE). However, IRF5 activation status during the disease course and the effects of IRF5 inhibition after disease onset are unclear. Here, we show that SLE patients in both the active and remission phase have aberrant activation of IRF5 and interferon-stimulated genes. Partial inhibition of IRF5 is superior to full inhibition of type I interferon signaling in suppressing disease in a mouse model of SLE, possibly due to the function of IRF5 in oxidative phosphorylation. We further demonstrate that inhibition of IRF5 via conditional Irf5 deletion and a newly developed small-molecule inhibitor of IRF5 after disease onset suppresses disease progression and is effective for maintenance of remission in mice. These results suggest that IRF5 inhibition might overcome the limitations of current SLE therapies, thus promoting drug discovery research on IRF5 inhibitors

発症早期ALS患者に対する超高用量メチルコバラミンの有効性・安全性について : ランダム化比較試験

Importance: Post hoc analysis in a phase 2/3 trial indicated ultra-high dose methylcobalamin slowed decline of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score at week 16 as well as at week 182, without increase of adverse events, in patients with amyotrophic lateral sclerosis (ALS) who were enrolled within 1 year from onset. Objective: To validate the efficacy and safety of ultra-high dose methylcobalamin for patients with ALS enrolled within 1 year of onset. Design: A multicenter, placebo-controlled, double-blind, randomized phase 3 trial with 12-week observation and 16-week randomized period, conducted from October 2017 to September 2019. Setting: Twenty-five neurology centers in Japan. Participants: Patients with ALS diagnosed within 1 year of onset by the updated Awaji criteria were initially enrolled. Of those, patients fulfilling the following criteria after 12-week observation were eligible for randomization: 1- or 2-point decrease in ALSFRS-R total score, a percent forced vital capacity over 60%, no history of noninvasive respiratory support and tracheostomy, and being ambulant. The target number was 64 in both methylcobalamin and placebo groups. Of 203 patients enrolled in the observation, 130 patients (age, 61.0 ± 11.7 years; female, 56) met the criteria and were randomly assigned through an electronic web-response system to methylcobalamin or placebo (65 for each). Of these, 129 patients were eligible for the full analysis set, and 126 completed the double-blind stage. Interventions: Intramuscular injection of methylcobalamin 50 mg or placebo twice weekly for 16 weeks. Main outcomes and measures: The primary endpoint was change in ALSFRS-R total score from baseline to week 16 in the full analysis set. Results: The least-squares mean difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo (−2.66 versus −4.63; 95% CI, 0.44–3.50; P = 0.012). The incidence of adverse events was similar between the two groups. Conclusions and relevance: Ultra-high dose methylcobalamin was efficacious in slowing functional decline and safe in the 16-week treatment period in ALS patients in the early stage and with moderate progression rate. Trial registration: UMIN-CTR Identifier: UMIN000029588 (umin.ac.jp/ctr); ClinicalTrials.gov Identifier: NCT03548311 (clinicaltrials.gov