The hypothesis that amyloid-β (Aβ) peptides are the primary cause of Alzheimer's disease (AD) remains the best supported theory of AD pathogenesis. Yet, many observations are inconsistent with the ...hypothesis. Aβ peptides are generated when amyloid precursor protein (APP) is cleaved by presenilins, a process that also produces APP intracellular domain (AICD). We previously generated AICD-overexpressing transgenic mice that showed abnormal activation of GSK-3β, a pathological feature of AD. We now report that these mice exhibit additional AD-like characteristics, including hyperphosphorylation and aggregation of tau, neurodegeneration and working memory deficits that are prevented by treatment with lithium, a GSK-3β inhibitor. Consistent with its potential role in AD pathogenesis, we find AICD levels to be elevated in brains from AD patients. The in vivo findings that AICD can contribute to AD pathology independently of Aβ have important therapeutic implications and may explain some observations that are discordant with the amyloid hypothesis.
A devastating aspect of Alzheimer's disease (AD) is the progressive deterioration of memory due to neuronal loss. Amyloid precursor protein (APP) occupies a central position in AD and APP-derived ...amyloid-beta (Abeta) peptides are thought to play a pivotal role in disease pathogenesis. Nonetheless, it is becoming clear that AD etiology is highly complex and that factors other than Abeta also contribute to AD pathogenesis. APP intracellular domain (AICD) is generated together with Abeta and we recently showed that AICD transgenic mice recapitulate pathological features of AD such as tau hyperphosphorylation, memory deficits and neurodegeneration without increasing the Abeta levels. Since impaired adult neurogenesis is shown to augment memory deficits in AD mouse models, here we examined the status of adult neurogenesis in AICD transgenic mice.
We previously generated transgenic mice co-expressing 59-residue long AICD fragment and its binding partner Fe65. Hippocampal progenitor cell proliferation was determined by BrdU incorporation at 1.5, 3 and 12 months of age. Only male transgenic and their respective wilt type littermate control mice were used. We find age-dependent decrease in BrdU incorporation and doublecortin-positive cells in the dentate gyrus of AICD transgenic mice suggesting impaired adult neurogenesis. This deficit resulted from decreased proliferation and survival, whereas neuronal differentiation remained unaffected. Importantly, this impairment was independent of Abeta since APP-KO mice expressing AICD also exhibit reduced neurogenesis. The defects in adult neurogenesis are prevented by long-term treatment with the non-steroidal anti-inflammatory agents ibuprofen or naproxen suggesting that neuroinflammation is critically involved in impaired adult neurogenesis in AICD transgenic mice.
Since adult neurogenesis is crucial for spatial memory, which is particularly vulnerable in AD, these findings suggest that AICD can exacerbate memory defects in AD by impairing adult neurogenesis. Our findings further establish that AICD, in addition to Abeta, contributes to AD pathology and that neuroinflammation plays a much broader role in AD pathogenesis than previously thought.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Forest aboveground biomass (AGB) measurement is a direct estimator of the live carbon stock of that forest region. Increasing emission and concentration of CO
2
is a global threat as it is a major ...cause of today’s global warming. The forest AGB is a live carbon sequester that plays a major role by absorbing atmospheric CO
2
. There are field-based measurement methods of AGB, but the main disadvantage is that they are primarily destructive. Several authors have undertaken AGB estimation using different remote sensing data types, but they are mostly not cost-effective for extensive study areas. We have created a cost-effective algorithm for AGB estimation using multispectral (MSS) data. In this study, Indian Remote-Sensing Satellite-P6 (IRS P6) Linear Imaging Self-Scanning Sensor-4 (LISS-IV) MSS data have been used for the analysis. The research has tried to estimate the AGB of different types of forests existing in the study area by using various vegetation indices and the gray-level co-occurrence matrix (GLCM) and created a hybrid methodology combining the vegetation indices and GLCM. Among all vegetation indices, the simple ratio (SR) highly correlates with AGB of pure deciduous and coniferous forests. In a mixed forest region, due to a mixture of two canopy stands, there is a mixture of foliage angle and optical scattering distribution. Therefore, modified simple ratio (MSR) becomes dominant in mixed forest AGB estimation. Previously there was no study to justify this GLCM texture parameter selection. In this study, we have justified the parameter selection of GLCM texture statistics. This parameter selection will help researchers choose the proper GLCM texture parameter for their study. Integration of GLCM textures with vegetation indices enhances the AGB model strength for all forest regions. The deciduous forest map gives validation
R
2
of 0.89 with an RMSE of 1.93 ton/pixel. The validation
R
2
of the Coniferous Forest map is 0.83 with an RMSE of 1.35 ton/pixel. There is a comparatively identifiable improvement in mixed forest with validation
R
2
of 0.96 and RMSE of 0.25 ton/pixel. This study shows AGB storage of deciduous forest has a maximum share over other forest region of Kalimpong forest.
In response to neurodegeneration, the adult mammalian brain activates a cellular cascade that results in reactive astrogliosis and microgliosis. The mechanism through which astrocytes become reactive ...and the physiological consequences of their activation in response to neurodegeneration is complex. While the activation and proliferation of astrocytes has been shown to occur during massive neuronal cell death, the functional relationship between these two events has not been clearly elucidated. Here we show that in response to kainic acid‐ (KA) induced neurodegeneration, the mitogen sonic hedgehog (SHH) is upregulated in reactive astrocytes. SHH activity peaks at 7 days and is accompanied by increased Gli activity and elevated proliferation in several cell types. To determine the functional role of SHH‐Gli signaling following KA lesions, we used a pharmacological approach to show that SHH secreted by astrocytes drives the activation and proliferation of astrocytes and microglia. The consequences of SHH‐Gli signaling in KA‐induced lesions appear to be independent of the severity of neurodegeneration. GLIA 2014;62:1595–1607
Main Points
The mitogen SHH is upregulated in reactive astrocytes in response to neurodegeneration, and it regulates astrocyte activation and proliferation.
Downstream targets of SHH‐Gli are activated in several cell types, and these targets are responsible for proliferation in postneurodegenerative lesions.
Amyloid precursor protein (APP) is cleaved by gamma-secretase to simultaneously generate amyloid beta (Aβ) and APP Intracellular Domain (AICD) peptides. Aβ plays a pivotal role in Alzheimer's disease ...(AD) pathogenesis but recent studies suggest that amyloid-independent mechanisms also contribute to the disease. We previously showed that AICD transgenic mice (AICD-Tg) exhibit AD-like features such as tau pathology, aberrant neuronal activity, memory deficits and neurodegeneration in an age-dependent manner. Since AD is a tauopathy and tau has been shown to mediate Aβ-induced toxicity, we examined the role of tau in AICD-induced pathological features. We report that ablating endogenous tau protects AICD-Tg mice from deficits in adult neurogenesis, seizure severity, short-term memory deficits and neurodegeneration. Deletion of tau restored abnormal phosphorylation of NMDA receptors, which is likely to underlie hyperexcitability and associated excitotoxicity in AICD-Tg mice. Conversely, overexpression of wild-type human tau aggravated receptor phosphorylation, impaired adult neurogenesis, memory deficits and neurodegeneration. Our findings show that tau is essential for mediating the deleterious effects of AICD. Since tau also mediates Aβ-induced toxic effects, our findings suggest that tau is a common downstream factor in both amyloid-dependent and-independent pathogenic mechanisms and therefore could be a more effective drug target for therapeutic intervention in AD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Reducing environmental pollution is a critical goal in global environmental economics and economic development. The European Union (EU) faces environmental challenges due to its development ...activities. Here we present a comprehensive approach to assess the impact of carbon dioxide (CO2) emissions, energy consumption (EC), population structure (POP), economy (GDP), and policies on the environment within the EU using the environmental Kuznets curve (EKC). Our research reveals that between 1990 and 2019, the EU-27 experienced an increase of +1.18 million tonnes of oil equivalent (Mtoe) per year in energy consumption (p < 0.05), while CO2 emissions decreased by 24.25 million tonnes (Mt) per year (p < 0.05). The highest reduction in CO2 emissions occurred in Germany (−7.52 Mt CO2 annually), and the lowest in Latvia (−0.087 Mt CO2 annually). The empirical EKC analysis shows an inverted-U shaped relationship between GDP and CO2 emissions in the EU-27. Specifically, a 1% increase in GDP results in a 0.705% increase in carbon emission, while a 1% increase in GDP2 leads to a 0.062% reduction in environmental pollution in the long run (p < 0.01). These findings indicate that economic development within the EU has reached a stage where economic growth positively impacts the environment. Overall, this study provides insights into the effectiveness of environmental policies in mitigating degradation and promoting green growth in the EU 27 countries.
•The total GHG emissions of the EU-27 were reduced significantly (p < 0.05).•The energy consumption increased significantly by +1.18 Mtoe per year (p < 0.05).•The Environmental Kuznets Curve relation has been confirmed within EU-27.•Economic development within the EU-27 has started to improve the environment.
In this study, the objective was to analyze the principal natural factors causing soil water erosion in the Oued El Ardjem basin. The approach was based on the use of a Geographic Information System ...(GIS) and Remote Sensing (RS), with the acquisition and processing of satellite images and cross-checking with other geospatial data in the GIS tool. Also, the use of multivariate statistics is an integral part of the current study. The main factors to be estimated were related to environmental conditions such as climate, soil, relief, and land use. According to the RUSLE (Revised Universal Soil Loss Equation), we produced a descriptive map of four classes of multifactorial soil sensitivity to water erosion: low (31.08%), medium (27.04%), high (20.50%), and very high (21.38%). The areas susceptible to erosion were found in fragile soils and substrates with steep slopes and/or undergoing very extensive agriculture where the plant cover levels were low and not very protective. This study provides a tool to help decision-makers better manage water and soil resources, considering the rural population’s expectations and needs. Spatio-temporal information of estimated water-induced soil erosion could help in soil conservation and management. We believe the study provides insight into erosion control and watershed management practices.
Water erosion is a major threat to biodiversity, according to the European Commission’s Soil Thematic Strategy, as it negatively affects soil structure, soil fertility and water availability for ...plants. The island of Crete (Southern Greece) has been characterized as a biodiversity hotspot including several Natura 2000 (N2K)-protected areas. The aim of this study was to model the soil loss rate in Crete regarding species richness, habitat types and their conservation status, as well as the MAES (Mapping and Assessment of Ecosystem and their Services) ecosystem types. To this end, the RUSLE soil erosion prediction model was implemented, using freely available geospatial data and cloud-computing processes. The estimated average soil loss in the study area was 6.15 t ha−1 y−1, while there was no significant difference between the terrestrial N2K (6.06 t ha−1 y−1) and non-N2K (6.19 t ha−1 y−1) areas. Notably, the natural habitats of principal importance for the conservation of biodiversity (referred to as “priority” areas), according to Annex I to Directive 92/43/EEC, are threatened by soil erosion with an estimated mean annual soil loss equal to 8.58 t ha−1 y−1. It is also notable that grasslands, heathland and shrubs and sparsely vegetated areas experienced the highest erosion rates among the identified MAES ecosystem types. The results showed that soil erosion is a serious threat to biodiversity in N2K-protected areas. Therefore, there is a need for systematic spatiotemporal monitoring and the implementation of erosion mitigation measures.
Kalimpong district, a part of the Darjeeling Himalaya, exhibits a variety of factors that are ideal for the occurrence of landslides. Therefore, it is imperative to demarcate the zones that are ...highly susceptible to landslide phenomena in advance, so that the risk, and hence the damage can be reduced to a significant extent through proper land-use planning. The factors that have been considered for this study are: (1) elevation, (2) slope, (3) aspect, (4) curvature, (5) distance to drainage, (6) soil type, (7) rainfall, (8) distance to lineaments, (9) landuse, (10) distance to road, (11) TWI, and (12) NDVI. For landslide susceptibility mapping of Kalimpong district, a resilient back propagation (Rprop) artificial neural networks (ANN) approach was used in this study. The results of the Rprop ANN model were validated using the AUC of the ROC Curves. The prediction rate AUC value was found to be 84.35% which showed that this combination of factors with the Rprop ANN model gave satisfactory accuracy in agreement with past landslide phenomena. The derived landslide susceptibility map was categorized in extremely low, low, moderate, high, and very high susceptibility zones covering 610, 272, 83, 61, and 66.7 km
2
of Kalimpong’s area, respectively.
Research highlights
Landslide Susceptibility Mapping (LSM) of Kalimpong, Eastern Himalaya.
A new improvised approach to LSM using Resilient Back Propagation ANN.
Different combination of 12 landslide factors with Rprop ANN.
High Prediction accuracy of Rprop ANN Model at 84.35%.
Quick and reliable LSM method for susceptible zone management.
Immediate early genes (IEG) such as c-Fos and Fos-related antigens (FRA) have been used as markers of neuronal activation. In this study, we determined whether the expression of c-Fos/FRAs is ...increased in the brains of adult male Acheta domesticus crickets following agonistic interactions. We looked for c-Fos/FRA proteins in the brain of un-fought, control male crickets and of dominant and subordinate male crickets sacrificed at different time periods following an agonistic interaction. Using immunoblot analysis, we found four different c-Fos/FRA-like proteins in the adult cricket brain. Continuous agonistic interaction increased c-Fos/FRA protein expression in the brains of subordinate males compared to control and dominant males. In addition, direct electrical stimulation of the male cricket antennae increased c-Fos/FRA-like protein in the brain. We identified the specific brain regions that exhibit c-Fos/FRA-like immunoreactivity in crickets. We detected c-Fos/FRA-like cellular immunoreactivity in different functional regions of the adult brain including the pars intercerebralis, protocerebrum, deutocerebrum, and the cortex of the mushroom bodies.
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