Apolipoprotein E4 (1–272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells

<p>Abstract</p> <p>Background</p> <p>Apolipoprotein E allele ε4 (apoE4) is a strong risk factor for developing Alzheimer's disease (AD). Secreted apoE has a critical function in redistributing lipids among central nervous system cells to maintain normal lipid homeostasis. In addition, previous reports have shown that apoE4 is cleaved by a protease in neurons to generate apoE4(1–272) fragment, which is associated with neurofibrillary tanglelike structures and mitochondria, causing mitochondrial dysfunction. However, it still remains unclear how the apoE fragment associates with mitochondria and induces mitochondrial dysfunction.</p> <p>Results</p> <p>To clarify the molecular mechanism, we carried out experiments to identify intracellular apoE-binding molecules and their functions in modulating mitochondria function. Here, we found that apoE4 binds to ubiquinol cytochrome <it>c </it>reductase core protein 2 (UQCRC2) and cytochrome C1, both of which are components of mitochondrial respiratory complex III, and cytochrome <it>c </it>oxidase subunit 4 isoform 1 (COX IV 1), which is a component of complex IV, in Neuro-2a cells. Interestingly, these proteins associated with apoE4(1–272) more strongly than intact apoE4(1–299). Further analysis showed that in Neuro-2a cells expressing apoE4(1–272), the enzymatic activities of mitochondrial respiratory complexes III and IV were significantly lower than those in Neuro-2a cells expressing apoE4(1–299).</p> <p>Conclusion</p> <p>ApoE4(1–272) fragment expressed in Neuro2a cells is associated with mitochondrial proteins, UQCRC2 and cytochrome C1, which are component of respiratory complex III, and with COX IV 1, which is a member of complex IV. Overexpression of apoE4(1–272) fragment impairs activities of complex III and IV. These results suggest that the C-terminal-truncated fragment of apoE4 binds to mitochondrial complexes and affects their activities, and thereby leading to neurodegeneration.</p

Sustainable Groundwater Management in Context of Climate Change in Northwest Bangladesh

The objectives of the study are to understand the variability and changes in hydro-climatic variables in space and time dimensions, and to evaluate the performance of managed aquifer recharge (MAR) for sustainable water resources management in northwest Bangladesh. The study reveals that groundwater resource in the northwest Bangladesh is under stress. The stress has developed and it increases over the years, as a result, shallow groundwater resource has already become scarce. The people of the area are not getting even drinking water using their hand tube wells (HTWs) during the dry season and facing trouble with irrigation water. These problems are becoming acute as a result of uncontrolled and unplanned groundwater abstraction for irrigation. Moreover, rainfall in the study area decreases and dryness increases. Higher values of the seasonality index ( SI ¯ = 0.87 ) and precipitation concentration index (PCI = 19.8) are indicators of frequent dry spells. The area suffered from 12 moderate-extreme droughts during 1971–2011, and moderate to high drought risk (B) prevails in the area. The frequent drought, decreasing trend in rainfall, transboundary river flow, and thick clay surface lithology along with the uncontrolled irrigation are also responsible for rapid depletion of groundwater. As the annual surplus of water (average = 594 mm) is higher than groundwater recharge (330 mm), an experimental study on managed aquifer recharge (MAR) has been conducted to enhance the groundwater recharge. It shows good performance for restoring the groundwater without creating any sorts of hazards. Moreover, almost 5% of irrigated land can be irrigated from surface water sources by re-excavating the rivers, Kharis (small channels). It is necessary to prepare an integrated water resource management plan (IWRMP) considering the impacts of climate change, drought risk, driving factors of the groundwater resource depletion, and rainwater as a resource for achieving the sustainability

Evaluations of the downward velocity of soil water movement in the unsaturated zone in a groundwater recharge area using δ18 O tracer: the Kumamoto region, southern Japan

Water and substances from the surface infiltrate the unsaturated zone before reaching groundwater. Yet, little study has been done on the unsaturated zone due to the difficulty of sampling. A lot of studies have been carried out on the top soil down to a depth of one metre and on shallow aquifers because they are easily accessible for sampling. The unsaturated zone of the Kumamotoregion recharge areas is important due to concerns about groundwater pollution from agriculture. The aim of this study was to estimate the downward velocity of soil water movement through the unsaturated zone and the recharge rate using δ18O as a tracer. Five sampling sites were selected and a core was taken from each site. The cores were cut into 0.1 m pieces and soil water was extracted from each to analyze for δD and the δ18O content. Average δD and δ18O compositions of soil water were similar to the isotopic compositions of summer precipitation. Annual average recharge rate and the downward velocity of soil water in each site were estimated by fitting a vertical δ18O profile pattern to a precipitation δ18O time series as a theoretical water displacement flow model for recharge. An estimated annual average recharge rate in the recharge area ranged from 745 to 1058 mm/yr with the annual average downward velocity of 1.37 to 2.34 m/yr. Based on the estimated downward velocity, the infiltration time for soilwater to reach the aquifer was determined as ranging from 9 to 24 years, which corresponds with previous groundwater age estimations presented in an earlier published study on the same area. It was assumed that contaminants will reach aquifers in 9 to 25 years if the effects of diffusion and microbiological reaction are not taken into account

Temporal characteristics of groundwater chemistry affected by the 2016 Kumamoto earthquake using self-organizing maps

Possibilities to perform pre- and post-seismic groundwater chemical comparisons on regional groundwater flow systems are rare due to lack of data and observations. The Kumamoto earthquake provides an unusual opportunity to improve the knowledge on earthquake hydrology and earthquake effects on hydrochemistry of groundwater due to a wealth of pre- and post-quake observations. We analyzed 12 physiochemical parameters (SiO2, (NO3 ? + NO2 ?)-N, Fetotal, Mntotal, pH, F?, Cl?, SO4 2?, Na+, K+, Ca2+, and Mg2+) using self-organizing maps (SOM) combined with hydrological and geological characteristics to improve the understanding of changes in groundwater chemistry after a major earthquake. The results indicate that the earthquake induced hydrological and environmental change via fault forming (Suizenji fault systems), liquefaction, rock fracturing, and ground shaking. These geological processes created rock fresh reactive surfaces, rock loosening, and enhancement of hydraulic conductivity. In turn, this lead to secondary processes in groundwater chemistry by advection, dilution, and chemical reaction. The most obvious indicator of hydrological and environmental change was from the increased dissolved silica content stemming from fracturing and Si-O bond cleavage in silicate rocks. Besides this, decreasing concentration of common ions (Cl?, F?, Na+, K+, Ca2+) was found due to dilution from mountain-side water release. Increase in (NO3 ? + NO2 ?)-N, SO4 2?, and Mg2+ concentration occurred locally due to soil leaching of contaminants or agricultural fertilizers through surface ruptures in recharge areas. Increase of SO4 2? content also originated from leaching of marine clay in coastal areas and possibly sporadic deep crustal fluid upwelling. Increase in (NO3 ? + NO2 ?)-N and Cl? content occurred from sewage water pipe breaks in the Suizenji fault formation in urban areas. Decrease of pH occurred in a few wells due to mixing of river water and different types of aquifer groundwater. Increase of Fetotal and Mntotal concentration possibly originated from leaching of marine clay by liquefaction in coastal areas. However, in most cases the water chemistry changes were subtle, thus not resulting in any groundwater quality deterioration of water supplies

Describing coseismic groundwater level rise using tank model in volcanic aquifers, Kumamoto, southern Japan

The change of groundwater levels after the 2016 Mw 7.0 Kumamoto crustal earthquake was evaluated using a simple conceptual hydrological model in an attempt to show the presence, intensity, and probable mechanism of water level rise observed in Kumamoto where a comprehensive observation-well network exists. A tank model was applied to verify 16 wells in the study field. In the model groundwater levels were first calibrated for the periods in ca. 2 years before the main shock using several hydrological parameters including precipitation, evapotranspiration, water recharge and discharge, and artificial recharge by irrigation. Water levels were then simulated by extrapolating this law of water fluctuating patterns for ca. 2.5 years after the main shock of the earthquake, without considering hydrogeological changes due to the earthquake. A difference in groundwater levels between observation and simulation results yields a degree of coseismic water level rises for each well. The coseismic abnormal water level increase was calculated to be ~11 m in 4?5 month after the main shock and was most significantly on the western slope of the Aso caldera rim mountains. The spatial distribution of the coseismic water increases clarified that the most dominate increasing anomalies prevail at mountain feet surrounding the plains, suggesting the occurrence of coseismic mountain water release resulting in the rise of water levels in downslope aquifers. Identified coseismic water level increases still continue up to 2.5 years after the earthquake, probably because changes in hydrogeological properties in mountain aquifers, i.e., permeability, are still sustained. Our forecasting water recovering trends require ca. 3.5?5 year after the earthquake for complete recovery to the original conditions. We demonstrated that our approaches are capable of describing coseismic water level changes and could potentially be applied to other fields

Estimating Groundwater Mixing Ratios from Vertical Flux Processes due to Excessive Groundwater Pumping Using Hydrogeochemical Parameters and Nitrate Concentrations in the Bandung Basin, Indonesia

One crucial task in groundwater research and management is the estimation of groundwater mixing ratios. Here, estimations of mixing ratios are presented systematically and spatially for shallow and deep groundwater in some areas of excessive groundwater pumping with different magnitudes of groundwater drawdown. The mixing ratios are estimated using two methods: (1) the total mixing ratio using all parameters, and (2) the mixing ratio using nitrate concentrations. The values for the total mixing ratio indicate that mixing between the shallow and the deep groundwater clearly occurs in all three depression areas, but with different ratios. The spatial distribution map of the total mixing ratio clearly shows that the largest mixing ratio occurs near the center of the cone of depression, and that the ratio decreases gradually away from the center of the depression area. There is a positive correlation among total mixing ratios, CFC-12 concentrations, and modeled vertical flux. Remarkably, the highest correlation is found between the correlation of the total mixing ratio and magnitude of vertical flux in the largest drawdown area. Meanwhile, comparison of the mixing ratio calculations by the different methods showed insignificant correlation which means nitrate is ineffective as the prevailing contaminant tracer for deep groundwater in this basin. Overall, this study concludes that the method of total mixing ratio using all chemical parameters is the most effective and consistent with previous methods. This study provides further proof that groundwater mixing between the shallow and deep groundwater systems has clearly occurred in the Bandung basin as an impact of excessive groundwater pumping.</p

Recovery of Lost Nexus Synergy via Payment for Environmental Services in Kumamoto, Japan

The objective of this study is to characterize and quantify the “trans-spatial nexus synergy” benefit of subsidized water ponding in the water-energy-food nexus in Kumamoto, Japan. After years of decreased rice production in upstream areas and associated declines in groundwater levels, the Kumamoto city government implemented a subsidy program whereby farmers in the Shira River basin receive payments to water their fields, which provides valuable groundwater recharge to downstream Kumamoto city. We quantify the economic benefits of this subsidy program, which include avoided additional energy costs to obtain scarcer levels of groundwater, as well as net revenue from the crops in the Shira River basin that would otherwise not be grown in the absence of the subsidy. These annual benefits can be combined and compared to the annual cost of the government subsidy. We also calculate potential historical losses that may have occurred in the region as a result of land use transitions from rice farming to urban use, which disrupted the nexus synergy between the watered fields and the groundwater table

Manual on the proper use of the 211At-labeled PSMA ligand ([211At]PSMA-5) for clinical trials of targeted alpha therapy (1st edition)

The version of record of this article, first published in Annals of Nuclear Medicine, is available online at Publisher’s website: https://doi.org/10.1007/s12149-024-01916-6.Recently, an astatine-labeled prostate-specific membrane antigen (PSMA) ligand ([211At]PSMA-5) has been developed for the targeted alpha therapy of patients with prostate cancer. This manual delineates its physicochemical characteristics to assist healthcare professionals in understanding the α-ray-emitting drug of [211At]PSMA-5 when administered to patients. The safety considerations regarding the handling and use of this drug in clinical trials are outlined, based on the proper usage manual of previous studies. The dose limits, as defined by the guidelines of the International Commission on Radiological Protection (ICRP) and the International Atomic Energy Agency (IAEA), are assessed for patients’ caregivers and the general public. According to the calculations provided in this manual, clinical trials involving [211At]PSMA-5 can be safely conducted for these populations even if patients are released after its administration. Moreover, this manual provides comprehensive guidance on the handling of [211At]PSMA-5 for healthcare facilities, and compiles a list of precautionary measures to be distributed among patients and their caregivers. While this manual was created by a research team supported by Ministry of Health, Labour, and Welfare in Japan and approved by Japanese Society of Nuclear Medicine, its applicability extends to healthcare providers in other countries. This manual aims to facilitate conducting clinical trials using [211At]PSMA-5 in patients with prostate cancer

Hydrogenated Borophene Shows Catalytic Activity as Solid Acid

Hydrogen boride (HB) or hydrogenated borophene sheets are recently realized two-dimensional materials that are composed of only two light elements, boron and hydrogen. However, their catalytic activity has not been experimentally analyzed. Herein, we report the catalytic activity of HB sheets in ethanol reforming. HB sheets catalyze the conversion of ethanol to ethylene and water above 493 K with high selectivity, independent of the contact time, and with an apparent activation energy of 102.8 ± 5.5 kJ/mol. Hence, we identify that HB sheets act as solid-acid catalysts