Hepatocyte cell death is a key process in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the factors responsible for and mechanisms underlying NASH-related cell death have not yet ...been elucidated in detail. We herein investigated the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (AGEs), named toxic AGEs (TAGE), on the production of reactive oxygen species (ROS), which have been implicated in the pathogenesis of NASH. Cell death related to intracellular TAGE accumulation was eliminated in the hepatocyte carcinoma cell line HepG2 by the antioxidant effects of N-acetyl-L-cysteine. The intracellular accumulation of TAGE increased ROS production and the expression of Nrf2, including its downstream gene. These results suggest that ROS are produced in association with the accumulation of TAGE and are a direct trigger for cell death. We also investigated the factors responsible for these increases in ROS. Catalase activity did not decrease with the accumulation of TAGE, while mitochondrial membrane depolarization was enhanced in cells treated with GA. These results indicate that TAGE play an important role in mitochondrial abnormalities and increases in ROS production, both of which are characteristic features of NASH. The suppression of TAGE accumulation has potential as a new therapeutic target in the progression of NASH.
Glacier mass loss is recognized as a major contributor to current sea level rise. However, large uncertainties remain in projections of glacier mass loss on global and regional scales. We present an ...ensemble of 288 glacier mass and area change projections for the 21st century based on 11 glacier models using up to 10 general circulation models and four Representative Concentration Pathways (RCPs) as boundary conditions. We partition the total uncertainty into the individual contributions caused by glacier models, general circulation models, RCPs, and natural variability. We find that emission scenario uncertainty is growing throughout the 21st century and is the largest source of uncertainty by 2100. The relative importance of glacier model uncertainty decreases over time, but it is the greatest source of uncertainty until the middle of this century. The projection uncertainty associated with natural variability is small on the global scale but can be large on regional scales. The projected global mass loss by 2100 relative to 2015 (79 ± 56 mm sea level equivalent for RCP2.6, 159 ± 86 mm sea level equivalent for RCP8.5) is lower than, but well within, the uncertainty range of previous projections.
Plain Language Summary
Melting glaciers (outside the large ice sheets in Greenland and Antarctica) contribute strongly to rising sea level and are expected to continue to do so throughout this century. However, the amount of future sea level rise from glaciers is not well known. One of the causes for uncertainty is the lack of knowledge of future greenhouse gas emissions. This uncertainty is growing steadily during the 21st century and constitutes the most important uncertainty by 2100. Another cause of uncertainty are the glacier models themselves, since they rely on approximations and simplifications of complex glacier processes. This uncertainty is very important until the middle of the 21st century, but less important in the second half of the 21st century. Overall, glaciers will lose around 18 % of their ice mass in a low‐emission scenario, or around 36 % in a high‐emission scenario, contributing roughly 79 or 159 mm to sea level rise by 2100.
Key Points
Glacier melt will contribute between 79 ± 56 (RCP2.6) and 159 ± 86 mm (RCP8.5) to sea level rise during 2015–2100
Until the mid‐21st century, disagreement between glacier models dominates the uncertainty
At the end of the 21st century, differing emission pathway choices made by human societies dominate the uncertainty
Coronary computed tomography angiography is widely used in clinical practice. Although 3-dimensional (D) volume rendering is useful for interpretation of coronary path and territory, 2D output is ...common for image interpretation. Most picture archiving and communication system is incapable of manipulating 3D due to insufficient graphic specification. Thus, 2D bull's eye map display is frequently used in cardiac imaging. We developed a bull's eye map which emulated the anatomical information of individual coronary path and dominancy.
Despite the importance of glacial lake development in ice dynamics and glacier thinning, in situ and satellite-based measurements from lake-terminating glaciers are sparse in the Bhutanese Himalaya, ...where a number of proglacial lakes exist. We acquired in situ and satellite-based observations across lake- and land-terminating debris-covered glaciers in the Lunana region, Bhutanese Himalaya. A repeated differential global positioning system survey reveals that thickness change of the debris-covered ablation area of the lake-terminating Lugge Glacier (-4.67±0.07 m a−1) is more than 3 times more negative than that of the land-terminating Thorthormi Glacier (-1.40±0.07 m a−1) for the 2004–2011 period. The surface flow velocities decrease down-glacier along Thorthormi Glacier, whereas they increase from the upper part of the ablation area to the terminus of Lugge Glacier. Numerical experiments using a two-dimensional ice flow model demonstrate that the rapid thinning of Lugge Glacier is driven by both a negative surface mass balance and dynamically induced ice thinning. However, the thinning of Thorthormi Glacier is minimised by a longitudinally compressive flow regime. Multiple supraglacial ponds on Thorthormi Glacier have been expanding since 2000 and have merged into a single proglacial lake, with the glacier terminus detaching from its terminal moraine in 2011. Numerical experiments suggest that the thinning of Thorthormi Glacier will accelerate with continued proglacial lake development.
To better understand the influence of topography on the formation of Himalayan debris-covered glaciers, we manually digitized 5301 glaciers, covering an area of 5691 ± 893 km2, from high-resolution ...Advanced Land Observing Satellite imagery, and identified 842 debris-covered glaciers with a debris-covered area of 3839 ± 753 km2. This estimation of the debris-covered area of these glaciers is a novel approach in the Eastern Himalayas. We investigated the relationship between the debris-covered area and the corresponding potential debris supply (PDS) slopes for the debris-covered glaciers across the region. The PDS slopes on the southern side show better correlation with their debris-covered area formation than those situated on the northern side of the Himalayan barrier, with this correlation weakening toward the western massifs. Further investigation showed that PDS slopes oriented SE to W exert a stronger control on the formation of debris-covered areas, which is related to the diurnal freeze–thaw cycle on the southern slope of the mountain barrier.
Objective
Deep learning approaches have attracted attention for improving the scoring accuracy in computed tomography-less single photon emission computed tomography (SPECT). In this study, we ...proposed a novel deep learning approach referring to positron emission tomography (PET). The aims of this study were to analyze the agreement of representative voxel values and perfusion scores of SPECT-to-PET translation model-generated SPECT (SPECT
SPT
) against PET in 17 segments according to the American Heart Association (AHA).
Methods
This retrospective study evaluated the patient-to-patient stress, resting SPECT, and PET datasets of 71 patients. The SPECT
SPT
generation model was trained (stress: 979 image pairs, rest: 987 image pairs) and validated (stress: 421 image pairs, rest: 425 image pairs) using 31 cases of SPECT and PET image pairs using an image-to-image translation network. Forty of 71 cases of left ventricular base-to-apex short-axis images were translated to SPECT
SPT
in the stress and resting state (stress: 1830 images, rest: 1856 images). Representative voxel values of SPECT and SPECT
SPT
in the 17 AHA segments against PET were compared. The stress, resting, and difference scores of 40 cases of SPECT and SPECT
SPT
were also compared in each of the 17 segments.
Results
For AHA 17-segment-wise analysis, stressed SPECT but not SPECT
SPT
voxel values showed significant error from PET at basal anterior regions (segments #1, #6), and at mid inferoseptal regions (segments #8, #9, and #10). SPECT, but not SPECT
SPT
, voxel values at resting state showed significant error at basal anterior regions (segments #1, #2, and #6), and at mid inferior regions (segments #8, #9, and #11). Significant SPECT overscoring was observed against PET in basal-to-apical inferior regions (segments #4, #10, and #15) during stress. No significant overscoring was observed in SPECTSPT at stress, and only moderate over and underscoring in the basal inferior region (segment #4) was found in the resting and difference states.
Conclusions
Our PET-supervised deep learning model is a new approach to correct well-known inferior wall attenuation in SPECT myocardial perfusion imaging. As standalone SPECT systems are used worldwide, the SPECT
SPT
generation model may be applied as a low-cost and practical clinical tool that provides powerful auxiliary information for the diagnosis of myocardial blood flow.
RecFOR and RecOR as Distinct RecA Loading Pathways Sakai, Akiko; Cox, Michael M.
Journal of biological chemistry/The Journal of biological chemistry,
01/2009, Letnik:
284, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The molecular role of the RecF protein in loading RecA protein onto single-stranded DNA (ssDNA)-binding protein-coated ssDNA has been obscured by the facility with which the RecO and RecR proteins ...alone perform this function. We now show that RecFOR and RecOR define distinct RecA loading functions that operate optimally in different contexts. RecFOR, but not RecOR, is most effective when RecF(R) is bound near an ssDNA/double-stranded (dsDNA) junction. However, RecF(R) has no enhanced binding affinity for such a junction. RecO and RecR proteins are both required under all conditions in which the RecFOR pathway operates. The RecOR pathway is uniquely distinguished by a required interaction between RecO protein and the ssDNA binding protein C terminus. The RecOR pathway is more efficient for RecA loading onto ssDNA when no proximal dsDNA is available. A merger of new and published results leads to a new model for RecFOR function.
The death of pancreatic islet β-cells (β-cells), which are the insulin-producing cells, promote the pathology in both Type 1 and Type 2 diabetes mellitus (DM) (T1DM and T2DM), and they are protected ...by autophagy which is one of the mechanisms of cell survival. Recently, that some advanced glycation end-products (AGEs), such as methylglyoxial-derived AGEs and
-carboxymethyllysine, induced the death of β-cells were revealed. In contrast, we had reported AGEs derived from glyceraldehyde (GA, the metabolism intermediate of glucose and fructose) are considered to be toxic AGEs (TAGE) due to their cytotoxicity and role in the pathogenesis of T2DM. More, serum levels of TAGE are elevated in patients with T1 and T2DM, where they exert cytotoxicity.
We researched the cytotoxicity of intracellular and extracellular TAGE in β-cells and the possibility that intracellular TAGE were associated with autophagy.
1.4E7 cells (a human β-cell line) were treated with GA, and analyzed viability, quantity of TAGE, microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, and p62. We also examined the viability of 1.4E7 cells treated with TAGE-modified bovine serum albumin, a model of TAGE in the blood.
Intracellular TAGE induced death of 1.4E7 cells, decrease of LC3-I, LC3-II, and p62. Extracellular TAGE didn't show cytotoxicity in the physiological concentration.
Intracellular TAGE induced death of β-cells more strongly than extracellular TAGE, and may suppress autophagy via reduction of LC3-I, LC3-II, and p62 to inhibit the degradation of them.
PDF
