Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

Decadal changes in the leading patterns of sea level pressure in the Arctic and their impacts on the sea ice variability in boreal summer

Besides its negative trend, the interannual and the interdecadal changes in the Arctic sea ice have also been pronounced in recent decades. The three leading modes in the sea level pressure (SLP) variability in the Arctic (70???90??????N) ??? the Arctic Oscillation (AO), the Arctic Dipole (AD), and the third mode (A3) ??? are analyzed to understand the linkage between sea ice variability and large-scale atmospheric circulation in boreal summer (June???August). This study also compares the decadal changes of the modes between the early (1982???1997) and the recent (1998???2017) periods and their influences on the Arctic sea ice extent (SIE). Only the AD mode shows a significant correlation increase with SIE in summer (JJA) from ???0.05 in the early period to 0.57 in the recent period. The AO and the A3 modes show a less significant relationship with SIE for the two periods. The AD is characterized by a dipole pattern of SLP, which modulates the strength of meridional surface winds and the Transpolar Drift Stream (TDS). The major circulation change in the late 1990s is that the direction of the wind has been changed more meridionally over the exit region of the Fram Strait, which causes sea ice drift and discharge through that region. In addition, the response of surface albedo and the net surface heat flux becomes larger and much clearer, suggesting a positive sea-ice???albedo feedback in the sea ice variability associated with the AD. The analysis also reveals that the zonal shift of the centers of SLP anomalies and associated circulation change affects a significant reduction in sea ice concentration over the Pacific sector of the Arctic Ocean. This study further suggests that the Pacific Decadal Oscillation (PDO) phase change could influence the spatial pattern change in the AD

Inter-Relationship Between Subtropical Pacific Sea Surface Temperature, Arctic Sea Ice Concentration, and the North Atlantic Oscillation in Recent Summers and Winters

The inter-relationship between subtropical western-central Pacific sea surface temperatures (STWCPSST), sea ice concentration in the Beaufort Sea (SICBS), and the North Atlantic Oscillation (NAO) are investigated for the last 37 summers and winters (1980-2016). Lag-correlation of the STWCPSST(-1) in spring with the NAO phase and SICBS in summer increases over the last two decades, reaching r = 0.4-0.5 with significance at 5 percent, while winter has strong correlations in approximately 1985-2005. Observational analysis and the atmospheric general circulation model experiments both suggest that STWCPSST warming acts to increase the Arctic geopotential height and temperature in the following season. This atmospheric response extends to Greenland, providing favorable conditions for developing the negative phase of the NAO. SIC and surface albedo tend to decrease over the Beaufort Sea in summer, linked to the positive surface net shortwave flux. Energy balance considering radiative and turbulent fluxes reveal that available energy that can heat surface is larger over the Arctic and Greenland and smaller over the south of Greenland, in response to the STWCPSST warming in spring. XXXX Arctic & Atlantic: Positive upper-level height/T anomaly over the Arctic and Greenland, and a negative anomaly over the central-eastern Atlantic, resembling the (-) phase of the NAO. Pacific: The negative height/T anomaly over the mid-latitudes, along with the positive anomaly over the STWCP, where 1degC warming above climatology is prescribed. Discussion: It is likely that the Arctic gets warm and the NAO is in the negative phase in response to the STWCP warming. But, there are other factors (e.g., internal variability) that contribute to determination of the NAO phase: not always the negative phase of the NAO in the event of STWCP warming (e.g.: recent winters and near neutral NAO in 2017 summer)

Elevated cellular cholesterol in Familial Alzheimer’s presenilin 1 mutation is associated with lipid raft localization of β-amyloid precursor protein

Familial Alzheimer’s disease (FAD)-associated presenilin 1 (PS1) serves as a catalytic subunit of γ-secretase complex, which mediates the proteolytic liberation of β-amyloid (Aβ) from β-amyloid precursor protein (APP). In addition to its proteolytic role, PS1 is involved in non-proteolytic functions such as protein trafficking and ion channel regulation. Furthermore, postmortem AD brains as well as AD patients showed dysregulation of cholesterol metabolism. Since cholesterol has been implicated in regulating Aβ production, we investigated whether the FAD PS1-associated cholesterol elevation could influence APP processing. We found that in CHO cells stably expressing FAD-associated PS1 ΔE9, total cholesterol levels are elevated compared to cells expressing wild-type PS1. We also found that localization of APP in cholesterol-enriched lipid rafts is substantially increased in the mutant cells. Reducing the cholesterol levels by either methyl-β-cyclodextrin or an inhibitor of CYP51, an enzyme mediating the elevated cholesterol in PS1 ΔE9-expressing cells, significantly reduced lipid raft-associated APP. In contrast, exogenous cholesterol increased lipid raft-associated APP. These data suggest that in the FAD PS1 ΔE9 cells, the elevated cellular cholesterol level contributes to the altered APP processing by increasing APP localized in lipid rafts

The Effect of Fish Consumption on Blood Mercury Levels of Pregnant Women

In the present study, we examined the relationship between average fish consumption, as well as the type of fish consumed and levels of mercury in the blood of pregnant women. We also performed follow-up studies to determine if blood mercury levels were decreased after counseling and prenatal education. To examine these potential relationships, pregnant women were divided into two groups: a study group was educated to restrict fish intake, whereas a control group did not receive any prenatal education regarding fish consumption. We measured blood mercury level and performed follow-up studies during the third trimester to examine any differences between the two groups. Out of the 63 pregnant women who participated in our study, we performed follow-up studies with 19 pregnant women from the study group and 12 pregnant women from control group. The average initial blood mercury level of both groups was 2.94 µg/L, with a range of 0.14 to 10.75 µg/L. Blood mercury level in the group who ate fish more than four times per month was significantly higher than that of the group who did not consume fish (p = 0.02). In follow-up studies, blood mercury levels were decreased in the study group but slightly increased in the control group (p = 0.014). The maternal blood mercury level in late pregnancy was positively correlated with mercury levels of cord blood (r = 0.58, p = 0.047), which was almost twice the level found in maternal blood. Pregnant women who consume a large amount of fish may have high blood mercury levels. Further, cord blood mercury levels were much higher than that of maternal blood. Because the level of fish intake appears to influence blood mercury level, preconceptual education might be necessary in order decrease fish consumption