Fact Sheet: Fossil Fuel Subsidies: A Closer Look at Tax Breaks and Societal Costs

The 116th Congress is weighing potential policy mechanisms to reduce the impact of climate change and cap global warming to an internationally agreed upon target of no more than 2 degrees Celsius (3.6 degrees Fahrenheit). As a result, fossil fuel tax subsidies, as well as other mechanisms of support, have received additional scrutiny from lawmakers and the public regarding their current suitability, scale and effectiveness. Indeed, the subsidies undermine policy goals of reducing greenhouse gas emissions from fossil fuels.The United States provides a number of tax subsidies to the fossil fuel industry as a means of encouraging domestic energy production. These include both direct subsidies to corporations, as well as other tax benefits to the fossil fuel industry. Conservative estimates put U.S. direct subsidies to the fossil fuel industry at roughly $20 billion per year; with 20 percent currently allocated to coal and 80 percent to natural gas and crude oil. European Union subsidies are estimated to total 55 billion euros annually

Synaptic tau: A pathological or physiological phenomenon?

In this review, we discuss the synaptic aspects of Tau pathology occurring during Alzheimer's disease (AD) and how this may relate to memory impairment, a major hallmark of AD. Whilst the clinical diagnosis of AD patients is a loss of working memory and long-term declarative memory, the histological diagnosis is the presence of neurofibrillary tangles of hyperphosphorylated Tau and Amyloid-beta plaques. Tau pathology spreads through synaptically connected neurons to impair synaptic function preceding the formation of neurofibrillary tangles, synaptic loss, axonal retraction and cell death. Alongside synaptic pathology, recent data suggest that Tau has physiological roles in the pre- or post- synaptic compartments. Thus, we have seen a shift in the research focus from Tau as a microtubule-stabilising protein in axons, to Tau as a synaptic protein with roles in accelerating spine formation, dendritic elongation, and in synaptic plasticity coordinating memory pathways. We collate here the myriad of emerging interactions and physiological roles of synaptic Tau, and discuss the current evidence that synaptic Tau contributes to pathology in AD.G.S.K.S. acknowledges funding from the Wellcome Trust (065807/Z/01/Z) (203249/Z/16/Z), the UK Medical Research Council (MRC) (MR/K02292X/1), Alzheimer Research UK (ARUK) (ARUK-PG013-14), Michael J Fox Foundation (16238) and Infnitus China Ltd. M.A.R acknowledges funding from the Engineering and Physical Sciences Research Council (EP/L015889/1)

Conceptualising comorbidity and multimorbidity in dementia: A scoping review and syndemic framework

BackgroundOlder people and people with dementia experience a high prevalence of multiple health conditions. The terms ‘comorbidity’ and ‘multimorbidity’ are often used interchangeably to describe this, however there are key conceptual differences between these terms and their definitions. This has led to issues in the validity and comparability of research findings, potentially inappropriate intervention development and differences in quality of health care.ObjectiveTo review how the terms ‘comorbidity’ and ‘multimorbidity’ are defined within peer-reviewed dementia research and propose an operational framework.DesignA scoping review of definitions within dementia research was carried out. Searches took place across five databases: Academic Search Premier, CINAHL Complete, MEDLINE, PsycARTICLES and PsycINFO. PRISMA-ScR guidelines were followed.ResultsContent analysis revealed five key themes, showing significant overlap and inconsistencies from both within, and between, the comorbidity and multimorbidity definitions; 1. Number of conditions; 2. Type of health conditions; 3. The co-occurrence of conditions; 4. The inclusion of an index disease (or not); 5. Use of medical language. The analysis also revealed gaps in how the underlying concepts of the definitions relate to people with dementia living with multiple health conditions.ConclusionThis scoping review found that current definitions of comorbidity and multimorbidity are heterogeneous, reductionist and disease-focussed. Recommendations are made on the design of research studies including transparency and consistency of any terms and definitions used. A syndemic framework could be a useful tool for researchers, clinicians and policy makers to consider a more holistic picture of a person with dementia’s health and wellbeing

Mechanism of synaptic vesicle retrieval in epilepsy

Excessive release of neurotransmitter is a characteristic of epileptogenic cells. A number of lines of evidence implicate defects in the synaptic vesicle cycle as a cause of this excessive release. Synaptic vesicles are retrieved by more than one route in central nerve terminals. During mild stimulation the dominant synaptic vesicle retrieval pathway is classical clathrin mediated endocytosis. During elevated neuronal activity retrieval of synaptic vesicle membrane by bulk endocytosis is the predominant retrieval method. As it is triggered by strong stimulation, bulk endocytosis may be of importance in retrieval during epilepsy, however little is currently known about this pathway. In order to investigate the role of bulk endocytosis, we sought to establish a cell culture model of epilepsy, to develop an assay to distinguish retrieval by bulk endocytosis, and to use these tools to look at the molecular players controlling this form of endocytosis. Characterisation of bulk endocytosis through the development of tailored assay systems has revealed that bulk endocytosis is a fast event that is triggered during strong stimulation. Bulk endocytosis provides the nerve terminal with an appropriate mechanism to meet the demands of synaptic vesicle retrieval during periods of intense synaptic vesicle exocytosis. Inhibition of a dephosphorylation specific dynamin I-syndapin I interaction by competitive peptides inhibits activity dependent bulk endocytosis, implicating this interaction in a role in this method of synaptic vesicle retrieval. Having characterised the strength of stimulation needed to activate bulk endocytosis, and the speed at which it occurs, we also investigated the effects of known anti-epileptogenic drugs on bulk endocytosis in our central nerve terminal model system

Detecting critical responses from deliberate self-harm videos on YouTube

YouTube is one of the leading social media platforms and online spaces for people who self-harm to search and view deliberate self-harm videos, share their experience and seek help via comments. These comments may contain information that signals a commentator could be at risk of potential harm. Due to a large amount of responses generated from these videos, it is very challenging for social media teams to respond to a vulnerable commentator who is at risk. We considered this issue as a multi-class problem and triaged viewers' comments into one of four severity levels. Using current state-of-the-art classifiers, we propose a model enriched with psycho-linguistic and sentiment features that can detect critical comments in need of urgent support. On average, our model achieved up to 60% precision, recall, and f1-score which indicates the effectiveness of the model

Pro-Inflammatory Priming of Umbilical Cord Mesenchymal Stromal Cells Alters the Protein Cargo of Their Extracellular Vesicles

From MDPI via Jisc Publications RouterHistory: accepted 2020-03-12, pub-electronic 2020-03-16Publication status: PublishedUmbilical cord mesenchymal stromal cells (UCMSCs) have shown an ability to modulate the immune system through the secretion of paracrine mediators, such as extracellular vesicles (EVs). However, the culture conditions that UCMSCs are grown in can alter their secretome and thereby affect their immunomodulatory potential. UCMSCs are commonly cultured at 21% O2 in vitro, but recent research is exploring their growth at lower oxygen conditions to emulate circulating oxygen levels in vivo. Additionally, a pro-inflammatory culture environment is known to enhance UCMSC anti-inflammatory potential. Therefore, this paper examined EVs from UCMSCs grown in normal oxygen (21% O2), low oxygen (5% O2) and pro-inflammatory conditions to see the impact of culture conditions on the EV profile. EVs were isolated from UCMSC conditioned media and characterised based on size, morphology and surface marker expression. EV protein cargo was analysed using a proximity-based extension assay. Results showed that EVs had a similar size and morphology. Differences were found in EV protein cargo, with pro-inflammatory primed EVs showing an increase in proteins associated with chemotaxis and angiogenesis. This showed that the UCMSC culture environment could alter the EV protein profile and might have downstream implications for their functions in immunomodulation

Synaptopathy:presynaptic convergence in frontotemporal dementia and amyotrophic lateral sclerosis

Frontotemporal dementia and amyotrophic lateral sclerosis are common forms of neurodegenerative disease that share overlapping genetics and pathologies. Crucially, no significantly disease-modifying treatments are available for either disease. Identifying the earliest changes that initiate neuronal dysfunction is important for designing effective intervention therapeutics. The genes mutated in genetic forms of frontotemporal dementia and amyotrophic lateral sclerosis have diverse cellular functions, and multiple disease mechanisms have been proposed for both. Identification of a convergent disease mechanism in frontotemporal dementia and amyotrophic lateral sclerosis would focus research for a targetable pathway, which could potentially effectively treat all forms of frontotemporal dementia and amyotrophic lateral sclerosis (both familial and sporadic).Synaptopathies are diseases resulting from physiological dysfunction of synapses, and define the earliest stages in multiple neuronal diseases, with synapse loss a key feature in dementia. At the presynapse, the process of synaptic vesicle recruitment, fusion and recycling is necessary for activity-dependent neurotransmitter release. The unique distal location of the presynaptic terminal means the tight spatio-temporal control of presynaptic homeostasis is dependent on efficient local protein translation and degradation.Recently, numerous publications have shown that mutations associated with frontotemporal dementia and amyotrophic lateral sclerosis present with synaptopathy characterized by presynaptic dysfunction. This review will describe the complex local signalling and membrane trafficking events that occur at the presynapse to facilitate neurotransmission and will summarize recent publications linking frontotemporal dementia/amyotrophic lateral sclerosis genetic mutations to presynaptic function. This evidence indicates that presynaptic synaptopathy is an early and convergent event in frontotemporal dementia and amyotrophic lateral sclerosis and illustrates the need for further research in this area, to identify potential therapeutic targets with the ability to impact this convergent pathomechanism

CDP-diacylglycerol phospholipid synthesis in detergent-soluble, non-raft, membrane microdomains of the endoplasmic reticulum

Phosphatidylinositol (PI) is essential for numerous cell functions and is generated by consecutive reactions catalyzed by CDP-diacylglycerol synthase (CDS) and PI synthase. In this study, we investigated the membrane organization of CDP-diacylglycerol synthesis. Separation of mildly disrupted A431 cell membranes on sucrose density gradients revealed cofractionation of CDS and PI synthase activities with cholesterol-poor, endoplasmic reticulum (ER) membranes and partial overlap with plasma membrane caveolae. Cofractionation of CDS activity with caveolae was also observed when low-buoyant density caveolin-enriched membranes were prepared using a carbonate-based method. However, immunoisolation studies determined that CDS activity localized to ER membrane fragments containing calnexin and type III inositol (1,4,5)-trisphosphate receptors but not to caveolae. Membrane fragmentation in neutral pH buffer established that CDP-diacylglycerol and PI syntheses were restricted to a subfraction of the calnexin-positive ER. In contrast to lipid rafts enriched for caveolin, cholesterol, and GM1 glycosphingolipids, the CDS-containing ER membranes were detergent soluble. In cell imaging studies, CDS and calnexin colocalized in microdomain-sized patches of the ER and also unexpectedly at the plasma membrane. These results demonstrate that key components of the PI pathway localize to nonraft, phospholipid-synthesizing microdomains of the ER that are also enriched for calnexin. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc

Final Report, Next-Generation Mega-Voltage Cargo-Imaging System for Cargo Conainer Inspection, March 2007

The UNLV Research Foundation, as the primary award recipient, teamed with Varian Medical Systems-Security & Inspection Products and the University of Nevada Las Vegas (UNLV) for the purpose of conducting research and engineering related to a "next-generation" mega-voltage imaging (MVCI) system for inspection of cargo in large containers. The procurement and build-out of hardware for the MVCI project has been completed. The K-9 linear accelerator and an optimized X-ray detection system capable of efficiently detecting X-rays emitted from the accelerator after they have passed through the device is under test. The Office of Science financial assistance award has made possible the development of a system utilizing a technology which will have a profound positive impact on the security of U.S. seaports. The proposed project will ultimately result in critical research and development advances for the "next-generation" Linatron X-ray accelerator technology, thereby providing a safe, reliable and efficient fixed and mobile cargo inspection system, which will very significantly increase the fraction of cargo containers undergoing reliable inspection as the enter U.S. ports. Both NNSA/NA-22 and the Department of Homeland Security's Domestic Nuclear Detection Office are collaborating with UNLV and its team to make this technology available as soon as possible

Spatial variation of the physical and biomechanical properties within an equestrian arena surface

There is limited information about spatial variation of equestrian arena surfaces despite unequivocal evidence to suggest that lack of uniformity increases risk of injury. Spatial differences in the functional properties of an arena are likely to be due to a number of intrinsic and extrinsic characteristics including variation in the physical properties of the surface. The aim of this work was to examine spatial variation of peak load (cushioning) across an arena surface and investigate the influence that physical properties had on these variations using Principal Component Analysis. Sampling (n=61) of a 20 m by 65 m indoor synthetic equestrian arena surface occurred in one day using an Orono biomechanical surface tester (OBST). The OBST was used at every location to measure peak load (dropped twice on the same point). A 200 g sample of the surface was taken from the point of impact (at every location) and the physical properties were assessed in the laboratory. Samples were oven dried at 45⁰C for 24 hours in order to measure moisture content and percentage binder was quantified using Soxhlet extraction. Sand particle size distribution were determined using sieving and sedimentation methods and percentage organic matter was achieved by burning off organic material using a muffle furnace at 440⁰C. The surface was characterized by three principal components (PC1, PC2 and PC3). Peak load and moisture were the first principal components that accounted for 41% of surface variation. Percentage organic matter and percentage binder were identified as PC2 (20%) and PC3 (18%) respectively. This highlights their respective importance in surface variation. There was a moderate negative correlation between moisture and peak load (rs = 54%; P<0.0001) however cluster analysis revealed that peak load and moisture were grouped into five areas of similarity that corresponded to sample location, reinforced using an ANOVA (P<0.0001). The findings demonstrate an effective method of assessing uniformity and additionally, identify physical factors relevant to the load carrying capacity of this specific surface. Uneven surfaces can influence horse and rider safety therefore recognizing appropriate techniques to monitor spatial variation and implement relevant maintenance, is of key importance to equestrian athletes