Recent studies of Asian glaciers have shown that glaciers in eastern Karakoram and West Kunlun have been slightly gaining mass while those in nearby Jammu Kashmir and Himalayas are losing mass, at ...rates of more than 0.5 m w.e.yr
and about 0.3 m w.e.yr
, respectively. Two possible explanations have been proposed for this difference in glacier behaviour: spatial heterogeneity in climate change (climatic forcing) or differing glacier responses to climate change (glacier response). However, neither explanation has strong supporting evidence. Here, we examine the glacial response by calculating the mass-balance sensitivity to temperature change in high-mountain Asia. In support of the glacier-response explanation, we find a strong correlation between observed glacier surface-elevation changes and mass-balance sensitivity of glaciers. The high coefficient of determination (R
= 0.61) suggests that spatially heterogeneous mass-balance sensitivity has more explanatory power than regionally different climate change for the recent contrasting glacier fluctuations in the high mountain Asia.
The original Glacier Area Mapping for Discharge from the Asian
Mountains (GAMDAM) glacier inventory was the first methodologically
consistent dataset for high-mountain Asia. Nonetheless, the GAMDAM ...inventory
underestimated glacier area, as it did not include steep ice- and
snow-covered slopes or shaded components. During revision of the inventory,
Landsat imagery free of shadow, cloud, and seasonal snow cover was selected
for the period 1990–2010, after which >90 % of the glacier
area was delineated. The updated GAMDAM inventory, comprised of 453 Landsat
images, includes 134 770 glaciers with a total area of 100 693±11 790 km2.
Cardiovascular disease (CVD) is a lifestyle-related disease (LSRD) and one of the largest public health issues. Risk factors for CVD correlate with an excessive intake of glucose and/or fructose, ...which has been shown to induce the production of advanced glycation end-products (AGEs). We previously identified AGEs derived from glyceraldehyde and named them toxic AGEs (TAGE) due to their cytotoxicities and relationship with LSRD. We also reported that extracellular TAGE in the vascular system may promote CVD and that serum TAGE levels are associated with risk factors for CVD. The mechanisms responsible for the onset and/or progression of CVD by extracellular TAGE or the above risk factors involve vascular disorders. In the present study, we revealed that rat primary cultured cardiomyocytes generated intracellular TAGE, which decreased beating rates and induced cell death. LC3-II/LC3-I, a factor of autophagy, also decreased. Although intracellular TAGE may be targets of degradation as cytotoxic proteins via autophagy, they may inhibit autophagy. Furthermore, the mechanisms by which intracellular TAGE decrease beating rates and induce cell death may involve the suppression of autophagy. The present results suggest that intracellular TAGE are generated in cardiomyocytes and directly damage them, resulting in CVD.
Objectives
We assessed whether an association exists between myocardial oxygenation and myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM), using blood-oxygen-level-dependent ...(BOLD) T2* cardiac magnetic resonance imaging (T2*-CMR) and T1 mapping.
Methods
T1 mapping and T2*-CMR data were collected from 55 HCM patients using a 3-T MR and were prospectively analyzed. T2*-CMR was conducted using the black blood, breath-hold, multi-echo, and gradient echo sequence. Over 10 min, inhalation of oxygen at the flow rate of 10 L/min, T2* for mid-septum was measured following room-air and oxygen inhalation, and ΔT2* ratio (T2*oxy-T2*air/T2*air, %) was calculated. During pre- and post-gadolinium enhancement, native T1 (ms) and extracellular volume fractions (ECV, %) were calculated at sites same as the T2* measurement. Hypoxia was defined as the segment with an absolute value of the ΔT2* ratio ≥ 10%.
Results
ΔT2* ratio was significantly higher for segments with native T1 ≥ 1290 ms than those with native T1 < 1290 ms (21 ± 32% vs. 8 ± 6%,
p
= 0.005). ΔT2* ratio was also significantly higher for segments with ECV ≥ 28% than those with ECV < 28% (21 ± 32% vs. 8 ± 8%,
p
= 0.0003). ROC curve analysis revealed that ΔT2* ratio could detect segments with native T1 ≥ 1290 ms and ECV ≥ 28% and c-statistics of 0.72 and 0.79. According to the multivariate logistic regression analysis results, ECV is an independent factor in hypoxia
(
odds ratio, 1.47; 95% confidence interval, 1.02–2.13;
p
< 0.05)
.
Conclusions
Analysis of BOLD T2*-CMR and T1 mapping revealed that ECV is strongly associated with ΔT2* ratio, suggesting that the onset of myocardial fibrosis is related to hypoxia in HCM patients.
Trial registration
Our study was approved by the ethics committee of our institute (#4036, registered on 21 July 2016)
Key Points
• Analysis of ΔT2* ratio and ECV with BOLD-T2* and T1 mapping revealed a strong association between myocardial fibrosis and hypoxia in HCM patients.
We aimed to investigate the pre-treatment characteristics and treatment responses of isolated and systemic cardiac sarcoidosis (ICS and SCS) from FDG-PET/CT studies and to compare the prognoses of ...the two groups.
FDG-PET/CT images taken before and after treatment of 31 ICS and 91 SCS patients were analyzed retrospectively. Treatment response and recurrence were determined from the course of FDG-PET/CT. Treatment response and the incidence of both recurrence and major adverse cardiac events (MACE) were assessed in 16 ICS and 35 SCS patients who had been treated for more than 2 years.
A focal uptake pattern was more often observed than a focal-on-diffuse uptake pattern in both the ICS (74.2%) and SCS (63.7%) groups. Right ventricular involvement was significantly more frequent in SCS than ICS (44.0% vs. 9.6%, p < .001). SUVmax, cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) were significantly higher in SCS than ICS (SUVmax, 9.1 ± 4.1 vs. 4.8 ± 2.1; CMV, 118.0 ± 111.3 ml vs. 68.3 ± 94.7 ml; CMA, 541.6 ± 578.7 MBq vs. 265.1 ± 396.0 MBq, p < .001). Treatment responses in the two groups were similar, and complete resolution of cardiac uptake after immunosuppressive treatment was obtained in 62.5% of ICS patients and 77.1% of SCS patients (not significantly different). Likewise, no significant difference was found in the incidence of recurrence (40.0% for ICS, 44.4% for SCS) or MACE (25.0% for ICS, 22.8% for SCS).
SCS patients had more active and extensive CS lesions than ICS patients before treatment, but the two groups showed similar treatment responses and prognoses.
Nonalcoholic steatohepatitis (NASH), the aggressive form of the most common chronic liver disease nonalcoholic fatty liver disease, is characterized by inflammation and damage in the liver. Although ...hepatocyte injury and cell death have been identified as cardinal pathological features of NASH, its pathogenesis has not yet been elucidated in detail. Immortalized cell lines and primary cultured cells have been used as in vitro models of NASH. However, these cells have several disadvantages, such as specialized characteristics by immortalization or limited growth potential. To overcome these difficulties and develop a strategy to analyze the pathology of NASH, we employed hepatocyte-like cells differentiated from human induced pluripotent stem cells (hiPSC-HLCs) as an in vitro model of NASH to clarify the intracellular effects of glyceraldehyde-derived advanced glycation end-products (AGEs), also named toxic AGEs (TAGE). The viability of hiPSC-HLCs decreased with the accumulation of TAGE in the cells, which was consistent with previous findings on human hepatocellular carcinoma cells and human primary cultured hepatocytes. In addition, the TAGE accumulation up-regulated the expression of inflammation-related genes (interleukin 6, interleukin 8, and monocyte chemoattractant protein-1) in hiPSC-HLCs. These results indicated that the accumulation of TAGE induced hiPSC-HLC cytotoxicity and inflammation, which are features of the pathology of NASH. Therefore, we suggest the use of hiPSC-HLCs as an important strategy for analyses of the pathology of NASH.
What are the main morphological factors that control the heterogeneous responses of debris-covered glaciers to climate change in the southern central Himalaya? A debate is open whether thinning rates ...on debris-covered glaciers are comparable to those of debris-free ones. Previous studies have adopted a deterministic approach, which is indispensable, but is also limiting in that only a few glaciers can be monitored. In this context, we propose a statistical analysis based on a wider glacier population as a complement to these deterministic studies. We analysed 28 glaciers situated on the southern slopes of Mt. Everest in the central southern Himalaya during the period 1992–2008. This study combined data compiled by three distinct studies for a common period and population of glaciers for use in a robust statistical analysis. Generally, surface gradient was the main morphological factor controlling the features and responses of the glaciers to climate change. In particular, the key points that emerged are as follows. 1) Reduced downstream surface gradient is responsible for increased glacier thinning. 2) The development of supraglacial ponds is a further controlling factor of glacier thinning: where supraglacial ponds develop, the glaciers register further surface lowering. 3) Debris coverage and thickness index were not found to be significantly responsible for the development of supraglacial ponds, changes in elevation, or shifts in snow line altitude.
•Downstream surface gradient is the main factor controlling changes in mass balance, surface, SLA, pond density.•Reduced downstream surface gradient is responsible for increased glacier thinning.•Where supraglacial ponds develop the glaciers register further glacier thinning.•Debris coverage and thickness were not found significantly responsible for changes in glacier elevation.
Membrane contact sites (MCSs) serve as a zone for nonvesicular lipid transport by oxysterol-binding protein (OSBP)-related proteins (ORPs). ORPs mediate lipid countertransport, in which two distinct ...lipids are transported counterdirectionally. How such lipid countertransport controls specific biological functions, however, remains elusive. We report that lipid countertransport by ORP10 at ER-endosome MCSs regulates retrograde membrane trafficking. ORP10, together with ORP9 and VAP, formed ER-endosome MCSs in a phosphatidylinositol 4-phosphate (PI4P)-dependent manner. ORP10 exhibited a lipid exchange activity toward its ligands, PI4P and phosphatidylserine (PS), between liposomes in vitro, and between the ER and endosomes in situ. Cell biological analysis demonstrated that ORP10 supplies a pool of PS from the ER, in exchange for PI4P, to endosomes where the PS-binding protein EHD1 is recruited to facilitate endosome fission. Our study highlights a novel lipid exchange at ER-endosome MCSs as a nonenzymatic PI4P-to-PS conversion mechanism that organizes membrane remodeling during retrograde membrane trafficking.
Rural decline is a global concern, and Ecosystem Services (ES) play a crucial role in both rural revitalization and the Human Well-being (HW) of residents. This study investigated 9 revitalization ...cases in Shandong province, China, employing both quantitative and qualitative methods. It confirmed the effect on HW based on ES, using a comprehensive assessment framework covering local ecosystem services contribution and economic/social effect derived from the Millennium Ecosystem Service Assessment (MA) and Japan Biodiversity Outlook (JBO) and consolidated variations into four ES dimensions from a HW perspective. As a result, 4 common types of rural revitalization were identified: (A) Large-scale Agriculture, (B) Local Specialty/Brand Making, (C) Industry Integration, and (D) Urbanization Village, based on actors, core industries, and key revitalization activities. According to interviews with local residents, the residents express high levels of satisfaction with revitalization activities. Using TOPSIS analysis, we found that urbanization-led revitalization (D) excels in “economic/social” dimensions but falls short in “Interaction with nature and health" and “Life and culture with nature." In contrast, agriculture-based revitalization activities (A and B) offer a more balanced impact across various ES dimensions. The well-being of residents varies depending on how they utilize and connect with nature. These findings underscore the potential of large-scale agricultural development to address rural population decline and suggest that fostering a positive exchange of ES, HW and capital between rural and urban areas can enhance the resilience of the rural-urban system. These insights are especially relevant for addressing the urban-rural imbalances in developing countries experiencing urban expansion and rural decline.
•4 common types of rural revitalization have been identified in Shandong, China.•Agriculture-based activities performed balanced effects on the dimensions of all ESs.•Overall satisfaction has seen an increase due to rural promotional activities.•Fostering flow of ES and HW can facilitate the resilience of coupled rural-urban system.
Advanced glycation end-products (AGEs) are produced by the non-enzymatic reaction of sugars with proteins. It has been revealed that glyceraldehyde-derived toxic AGEs (TAGE) are elevated in the serum ...of non-alcoholic steatohepatitis (NASH) patients. NASH causes liver fibrosis and progresses to cirrhosis and hepatocellular carcinoma. However, the impact of TAGE in liver fibrosis caused by extracellular matrix accumulation remains poorly understood. In this study, we examined the effect of TAGE on the activation of hepatic stellate cells that are involved in liver fibrosis. LX-2 cells treated with transforming growth factor-β1 (TGF-β1) significantly reduced cell viability by apoptosis. However, the decrease in cell viability with TGF-β1 treatment was significantly suppressed by TAGE co-treatment. The levels of α-smooth muscle actin (α-SMA) and platelet-derived growth factor (PDGF)-Rβ and its ligand PDGF-B were increased in LX-2 cells following TGF-β1 treatment, suggesting that these cells were activated; however, these increases were unaffected by TAGE co-treatment. Moreover, collagen I level was increased with TGF-β1 treatment, and this increase was further increased by TAGE co-treatment. These results suggested that the suppression of apoptosis in activated LX-2 cells by TGF-β1 and TAGE co-treatment is related to an increase in the production of the extracellular matrix such as collagen I. Therefore, it was suggested that TAGE might aggravate the liver fibrosis of chronic hepatitis, such as NASH.
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