Guards and Culprits in the Endoplasmic Reticulum: Glucolipotoxicity and β-Cell Failure in Type II Diabetes

The endoplasmic reticulum (ER) is a cellular organelle responsible for multiple important cellular functions including the biosynthesis and folding of newly synthesized proteins destined for secretion, such as insulin. The ER participates in all branches of metabolism, linking nutrient sensing to cellular signaling. Many pathological and physiological factors perturb ER function and induce ER stress. ER stress triggers an adaptive signaling cascade, called the unfolded protein response (UPR), to relieve the stress. The failure of the UPR to resolve ER stress leads to pathological conditions such as β-cell dysfunction and death, and type II diabetes. However, much less is known about the fine details of the control and regulation of the ER response to hyperglycemia (glucotoxicity), hyperlipidemia (lipotoxicity), and the combination of both (glucolipotoxicity). This paper considers recent insights into how the response is regulated, which may provide clues into the mechanism of ER stress-mediated β-cell dysfunction and death during the progression of glucolipotoxicity-induced type II diabetes

Weekly Cycle of Lightning and Associated Patterns of Rainfall, Cloud, and Aerosols over Korea and Adjacent Oceans during Boreal Summer

In this study, we analyze the weekly cycle of lightning over Korea and adjacent oceans and associated variations of aerosols, clouds, precipitation, and atmospheric circulations, using aerosol optical depth (AOD) from the NASA Moderate resolution Imaging Spectroradiometer (MODIS) and Multi-angle Imaging SpectroRadiometer (MISR), cloud properties from MODIS, precipitation and storm height from Tropical Rainfall Measuring Mission (TRMM) satellite, and lightning data from the Korean Lightning Detection Network (KLDN) during 9-year from 2002 to 2010. Lightning data was divided into three approximately equal areas, land area of Korea, and two adjacent oceans, Yellow Sea and South Sea. Preliminary results show that the number of lightning increases during the middle of the week over Yellow Sea. AOD data also shows moderately significant midweek increase at about the same time as lightning peaks. These results are consistent with the recent studies showing the invigoration of storms with more ice hydrometeors by aerosols, and subsequently wash out of aerosols by rainfall. Frequency of lightning strokes tend to peak at weekend in land area and over South Sea, indicating local weekly anomalous circulation between land and adjacent ocean. On the other hand, lightning frequency over Yellow Sea appears to have very strong weekly cycle with midweek peak on around Wednesday. It is speculated that the midweek peak of lightning over Yellow Sea was related with aerosol transport from adjacent land area. AOD data also suggests midweek peak over Yellow Sea, however, the weekly cycle of AOD was not statistically significant. Changes in weekly cycle of lightning from pre-monsoon to monsoon season, as well as associated clouds and circulation patterns are also discussed

Tgif1 Counterbalances The Activity Of Core Pluripotency Factors In Mouse Embryonic Stem Cells

Core pluripotency factors, such as Oct4, Sox2, and Nanog, play important roles in maintaining embryonic stem cell (ESC) identity by autoregulatory feedforward loops. Nevertheless, the mechanism that provides precise control of the levels of the ESC core factors without indefinite amplification has remained elusive. Here, we report the direct repression of core pluripotency factors by Tgif1, a previously known terminal repressor of TGF beta/activin/nodal signaling. Overexpression of Tgif1 reduces the levels of ESC core factors, whereas its depletion leads to the induction of the pluripotency factors. We confirm the existence of physical associations between Tgif1 and Oct4, Nanog, and HDAC1/2 and further show the level of Tgif1 is not significantly altered by treatment with an activator/inhibitor of the TGF beta/activin/nodal signaling. Collectively, our findings establish Tgif1 as an integral member of the core regulatory circuitry of mouse ESCs that counterbalances the levels of the core pluripotency factors in a TGF beta/activin/nodal-independent manner.Cancer Prevention Research Institute of Texas (CPRIT) R1106Molecular Bioscience

Endoplasmic Reticulum Stress and Insulin Biosynthesis: A Review

Insulin resistance and pancreatic beta cell dysfunction are major contributors to the pathogenesis of diabetes. Various conditions play a role in the pathogenesis of pancreatic beta cell dysfunction and are correlated with endoplasmic reticulum (ER) stress. Pancreatic beta cells are susceptible to ER stress. Many studies have shown that increased ER stress induces pancreatic beta cell dysfunction and diabetes mellitus using genetic models of ER stress and by various stimuli. There are many reports indicating that ER stress plays an important role in the impairment of insulin biosynthesis, suggesting that reduction of ER stress could be a therapeutic target for diabetes. In this paper, we reviewed the relationship between ER stress and diabetes and how ER stress controls insulin biosynthesis

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

Avifauna of Bangtaesan Mountain, Gangwon-do, Korea

AbstractAn investigation on avifauna of the Bangtaesan Mountain was carried out from February until November, 2010 and it drew the results as follow. The number of birds observed in the whole Bangtaesan Mountain region was 989 individuals of 51 species (Maximum counts). Considering the results from literature research in addition, at least 90 species 1,000 individuals are thought to live in this region. In result, dominant species proved to be Yellow-throated Bunting (Emberiza elegans), Marsh Tit (Parus palustris), Azure-winged Magpie (Cyanopica cyana), Eastern Crowned Willow Warbler (Phylloscopus coronatus), Varied Tit (Parus varius), and more. Most of birds breeding in the forest of Korea were found to constitute these dominant bird species. Entire species diversity index appeared to be 3.35 relatively a high level; 3.34 in the south slopes while 3.22 in the north slopes showing relatively a high level in the south. Of them, 12 species including Mandarin Duck (Aix galericulata) were the Protected Birds species nominated and protected by the Cultural Heritage Administration or the Ministry of Environment, while 10 and 6 species were the natural monument species and endangered species level, respectively. Should further consistent surveys be carried out, a broader range of species would be found to breed, and therefore the Bangtaesan Mountain region including the area where the protected species are observed is believed to need a conservation and management through protected area designation

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