40 research outputs found
Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease
No full textHyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer(199-202)>pSer(214)>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss
Socioeconomic Impact Evaluation for Near Real-Time Flood Detection in the Lower Mekong River Basin
No full textFlood events pose a severe threat to communities in the Lower Mekong River Basin. The combination of population growth, urbanization, and economic development exacerbate the impacts of these events. Flood damage assessments, critical for understanding the effects of flooding on the local population and informing decision-makers about future risks, are frequently used to quantify the economic losses due to storms. Remote sensing systems provide a valuable tool for monitoring flood conditions and assessing their severity more rapidly than traditional post-event evaluations. The frequency and severity of extreme flood events are projected to increase, further highlighting the need for improved flood monitoring and impact analysis. In this study we integrate a socioeconomic damage assessment model with a near real-time flood remote sensing and decision support tool (NASA’s Project Mekong). Direct damages to populations, infrastructure, and land cover are assessed using the 2011 Southeast Asian flood as a case study. Improved land use/land cover and flood depth assessments result in rapid loss estimates throughout the Mekong River Basin. Results suggest that rapid initial estimates of flood impacts can provide valuable information to governments, international agencies, and disaster responders in the wake of extreme flood events
Impacts of representing sea-level rise uncertainty on future flood risks: An example from San Francisco Bay.
No full textRising sea levels increase the probability of future coastal flooding. Many decision-makers use risk analyses to inform the design of sea-level rise (SLR) adaptation strategies. These analyses are often silent on potentially relevant uncertainties. For example, some previous risk analyses use the expected, best, or large quantile (i.e., 90%) estimate of future SLR. Here, we use a case study to quantify and illustrate how neglecting SLR uncertainties can bias risk projections. Specifically, we focus on the future 100-yr (1% annual exceedance probability) coastal flood height (storm surge including SLR) in the year 2100 in the San Francisco Bay area. We find that accounting for uncertainty in future SLR increases the return level (the height associated with a probability of occurrence) by half a meter from roughly 2.2 to 2.7 m, compared to using the mean sea-level projection. Accounting for this uncertainty also changes the shape of the relationship between the return period (the inverse probability that an event of interest will occur) and the return level. For instance, incorporating uncertainties shortens the return period associated with the 2.2 m return level from a 100-yr to roughly a 7-yr return period (∼15% probability). Additionally, accounting for this uncertainty doubles the area at risk of flooding (the area to be flooded under a certain height; e.g., the 100-yr flood height) in San Francisco. These results indicate that the method of accounting for future SLR can have considerable impacts on the design of flood risk management strategies
Altered Expression of the CB1 Cannabinoid Receptor in the Triple Transgenic Mouse Model of Alzheimer's Disease
No full textThe endocannabinoid system has gained much attention as a new potential pharmacotherapeutic target in various neurodegenerative diseases, including Alzheimer's disease (AD). However, the association between CB1 alterations and the development of AD neuropathology is unclear and often contradictory. In this study, brain CB1 mRNA and CB1 protein levels were analyzed in 3 × Tg-AD mice and compared to wild-type littermates at 2, 6 and 12 months of age, using in-situ hybridization and immunohistochemistry, respectively. Semiquantitative analysis of CB1 expression focused on the prefrontal cortex (PFC), prelimbic cortex, dorsal hippocampus (DH), basolateral amygdala complex (BLA), and ventral hippocampus (VH), all areas with high CB1 densities that are strongly affected by neuropathology in 3 × Tg-AD mice. At 2 months of age, there was no change in CB1 mRNA and protein levels in 3 × Tg-AD mice compared to Non-Tg mice in all brain areas analyzed. However, at 6 and 12 months of age, CB1 mRNA levels were significantly higher in PFC, DH, and BLA, and lower in VH in 3 × Tg-AD mice compared to wild-type littermates. CB1 immunohistochemistry revealed that CB1 protein expression was unchanged in 3 × Tg-AD at 2 and 6 months of age, while a significant decrease in CB1 receptor immunoreactivity was detected in the BLA and DH of 12-month-old 3 × Tg-AD mice, with no sign of alteration in other brain areas. The altered CB1 levels appear, rather, to be age-and/or pathology-dependent, indicating an involvement of the endocannabinoid system in AD pathology and supporting the ECS as a potential novel therapeutic target for treatment of AD
Data_Sheet_1_The Value of Near Real-Time Earth Observations for Improved Flood Disaster Response.pdf
No full textInformation is a critical resource in disaster response scenarios. Data regarding the geographic extent, severity, and socioeconomic impacts of a disaster event can help guide emergency responders and relief operations, particularly when delivered within hours of data acquisition. Information from remote observations provides a valuable tool for assessing conditions “on the ground” more quickly and efficiently. Here, we evaluate the social value of a near real-time flood impact system using a disaster response case study, and quantify the Value of Information (VOI) of satellite-based observations for rapid response using a hypothetical flooding disaster in Bangkok, Thailand. MODIS imagery from NASA's Land, Atmosphere Near real-time Capability for EOS (LANCE) system is used to produce operational estimates of inundation depths and economic damages. These rapid Earth observations are coupled with a decision-analytical model to inform decisions on emergency vehicle routing. Emergency response times from vehicles routed using flood damage data are compared with baseline routes without the benefit of advance information on road conditions. Our results illustrate how the application of near real-time Earth observations can improve the response time and reduce potential encounters with flood hazards when compared with baseline routing strategies. Results indicate a potential significant economic benefit (i.e., millions of dollars) from applying near real-time Earth observations for improved flood disaster response and management.</p
Altered expression of Alzheimer's disease-related proteins in male hypogonadal mice
No full textAge-related depletion of estrogens and androgens is associated with an increase in Alzheimer's disease (AD) brain pathology and diminished cognitive function. Here we investigated AD-associated molecular and cellular changes in brains of aged hypogonadal (hpg) male and female mice. hpg Mice have a spontaneous, inactivating genetic mutation in the GnRH gene resulting in lifelong deficiency of gonadotropins and gonadal sex hormones. Western blot analysis revealed low levels of amyloid precursor protein and high levels of presenilin 1, amyloid precursor protein C-terminal fragment, and beta-amyloid 42 in brains of aged male, but not female, hpg mice. Changes were confined to the hippocampus and were not evident in the cerebellum or other brain tissues. Male hpg mice tended to have lower levels of IL-1 beta protein than male littermate controls. Immunohistochemical staining of the basal forebrain revealed that male hpg mice had lower choline acetyltransferase levels per neuron compared with controls. These AD-like changes specific to male hpg mice supports a link between androgen depletion and the development of AD pathology
Author Correction: Morphological Neural Computation Restores Discrimination of Naturalistic Textures in Trans-radial Amputees (Scientific Reports, (2020), 10, 1, (527), 10.1038/s41598-020-57454-4)
No full textIn the original version of this Article Paolo M. Rossini was incorrectly affiliated with ‘Institute of Neurology, Catholic University of The Sacred Heart, Policlinic A. Gemelli Foundation, Roma, Italy’. The correct affiliation is listed below. Brain Connectivity Laboratory, IRCCS San Raffaele Pisana, Roma, Italy. The original Article has been corrected
Data_Sheet_1_Deep Convolutional LSTM for improved flash flood prediction.docx
No full textFlooding remains one of the most devastating and costly natural disasters. As flooding events grow in frequency and intensity, it has become increasingly important to improve flood monitoring, prediction, and early warning systems. Recent efforts to improve flash flood forecasts using deep learning have shown promise, yet commonly-used techniques such as long short term memory (LSTM) models are unable to extract potentially significant spatial relationships among input datasets. Here we propose a hybrid approach using a Convolutional LSTM (ConvLSTM) network to predict stream stage heights using multi-modal hydrometeorological remote sensing and in-situ inputs. Results suggest the hybrid network can more effectively capture the specific spatiotemporal landscape dynamics of a flash flood-prone catchment relative to the current state-of-the-art, leading to a roughly 26% improvement in model error when predicting elevated stream conditions. Furthermore, the methodology shows promise for improving prediction accuracy and warning times for supporting local decision making.</p
Deep Convolutional LSTM for improved flash flood prediction
No full textFlooding remains one of the most devastating and costly natural disasters. As flooding events grow in frequency and intensity, it has become increasingly important to improve flood monitoring, prediction, and early warning systems. Recent efforts to improve flash flood forecasts using deep learning have shown promise, yet commonly-used techniques such as long short term memory (LSTM) models are unable to extract potentially significant spatial relationships among input datasets. Here we propose a hybrid approach using a Convolutional LSTM (ConvLSTM) network to predict stream stage heights using multi-modal hydrometeorological remote sensing and in-situ inputs. Results suggest the hybrid network can more effectively capture the specific spatiotemporal landscape dynamics of a flash flood-prone catchment relative to the current state-of-the-art, leading to a roughly 26% improvement in model error when predicting elevated stream conditions. Furthermore, the methodology shows promise for improving prediction accuracy and warning times for supporting local decision making
Consequences of the interaction of amyloid beta with amyloid binding alcohol dehydrogenase and the receptor for advanced glycation end products
No full textAmyloid beta (Aβ) has been postulated to be the principle initiator of the pathogenesis of Alzheimer’s disease (AD). Therefore, understanding the underlying mechanisms of Aβ induced neurotoxicity in the early stages of AD would be essential for finding potential therapeutic targets of AD.
Aβ-binding alcohol dehydrogenase (ABAD) has been shown to be a mitochondrial binding site for Aβ. Expression of ABAD has been found to be increased in brains of AD sufferers. Two dimensional electrophoresis studies have revealed that endophilin 1 was upregulated in Tg mAPP/ABAD mice brains as compared to Tg mAPP, Tg ABAD and non-Tg mice brains. Increased expression of endophilin 1 has also been found in brains of AD patients as compared to non-demented control brain tissues. Endophilin1 has been reported to regulate c-Jun N-terminal kinase (JNK) activation. In this study, expression of dominant negative forms of endophilin 1 (DN-endophilin 1) in mouse cortical neurons exhibited a significant reduction of Aβ induced JNK activation. Furthermore, using cell counting methods, it was shown that the transfection of DN-endophilin 1 increased neuron survival after Aβ treatment.
Aβ has also been proposed to disrupt the interaction of ABAD and Cyclophilin D (CypD), which would trigger mitochondrial permeable transition, thereby leading to neurotoxicity. For fluorescence resonance energy transfer (FRET) analysis of the interaction of ABAD and CypD, a mitochondria targeted, EYFP tagged ABAD plasmid (pMito-ABAD-EYFP) and an ECFP tagged CypD (pCypD-ECFP) plasmid were developed. Positive FRET signals in SK-N-SH cells co-expressing pMito-ABAD-EYFP and pCypD-ECFP indicated that ABAD interacts with CypD in the mitochondria of mammalian cells.
RAGE (receptor for advanced glycation end products) has been reported to bind to Aβ and mediate the toxic effects of Aβ peptides on neurons and microglia. It has been shown previously that Tg mAPP/DN-RAGE mice display preserved cognitive function as compared to Tg mAPP mice. To investigate possible mechanisms involved in rescuing cognitive function by RAGE blockage, two dimensional electrophoresis was used to analyze differential protein expression between Tg mAPP and Tg mAPP/DN-RAGE mice cortex. Altered expression of four proteins, including NADH dehydrogenase flavoprotein 2 (NDUFV2), glyoxalase 1 (GLO1), proteasome subunit beta type 4 (PSMB4, or β7 subunit of proteasome) and nitrilase family, member 2 (Nit2) have been observed between Tg mAPP/DN-RAGE mice cortex and Tg mAPP mice cortex. NDUFV2 is a 24kDa subunit of complex 1 which is involved in ATP synthesis. GLO1 is a cytosolic enzyme that plays a role the glutathione-dependent detoxification of α-oxoaldehydes, such as methylglyoxal. PSMB4 is a subunit of the 26s proteosome which is in the degradation of ubiquitinylated proteins. The function of Nit2 is still unclear
