Astrocyte dysfunction in Alzheimer disease Acosta, Crystal; Anderson, Hope D.; Anderson, Christopher M.
Journal of neuroscience research,
December 2017, Letnik:
95, Številka:
12
Journal Article
Marine fish stocks are an important part of the world food system and are particularly important for many of the poorest people of the world. Most existing analyses suggest overfishing is increasing, ...and there is widespread concern that fish stocks are decreasing throughout most of the world. We assembled trends in abundance and harvest rate of stocks that are scientifically assessed, constituting half of the reported global marine fish catch. For these stocks, on average, abundance is increasing and is at proposed target levels. Compared with regions that are intensively managed, regions with less-developed fisheries management have, on average, 3-fold greater harvest rates and half the abundance as assessed stocks. Available evidence suggests that the regions without assessments of abundance have little fisheries management, and stocks are in poor shape. Increased application of area-appropriate fisheries science recommendations and management tools are still needed for sustaining fisheries in places where they are lacking.
Plant disease outbreaks are increasing and threaten food security for the vulnerable in many areas of the world. Now a global human pandemic is threatening the health of millions on our planet. A ...stable, nutritious food supply will be needed to lift people out of poverty and improve health outcomes. Plant diseases, both endemic and recently emerging, are spreading and exacerbated by climate change, transmission with global food trade networks, pathogen spillover, and evolution of new pathogen lineages. In order to tackle these grand challenges, a new set of tools that include disease surveillance and improved detection technologies including pathogen sensors and predictive modeling and data analytics are needed to prevent future outbreaks. Herein, we describe an integrated research agenda that could help mitigate future plant disease pandemics.
We characterize the ecological, economic, and community performance of 21 major tuna fisheries, accounting for at least 77% of global tuna production, using the Fishery Performance Indicators. Our ...analysis reveals that the biggest variations in performance among tuna fisheries are driven by the final markets that they target: international sashimi market tuna fisheries considerably outperform a comparison set of 62 non-tuna fisheries in the Fishery Performance Indicator database, international canned tuna market fisheries perform similarly to the comparison set, and tuna fisheries supplying local markets in coastal states considerably underperform the comparison set. Differences among regional fishery management organizations primarily reflect regional species composition and market access, despite stark variation in governance, management, and other enabling conditions. With a legacy of open access, tuna's harvest sector performance is similar across all fisheries, reflecting only a normal return on the capital and skill invested: industrial vessels slightly outperform semi-industrial and artisanal vessels. Differences emerge in the post-harvest sector however, as value chains able to preserve quality and transport fish to high value markets outperform others.
Pursuit of the triple bottom line of economic, community and ecological sustainability has increased the complexity of fishery management; fisheries assessments require new types of data and analysis ...to guide science-based policy in addition to traditional biological information and modeling. We introduce the Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for assessing performance in individual fisheries, and for establishing cross-sectional links between enabling conditions, management strategies and triple bottom line outcomes. Conceptually separating measures of performance, the FPIs use 68 individual outcome metrics--coded on a 1 to 5 scale based on expert assessment to facilitate application to data poor fisheries and sectors--that can be partitioned into sector-based or triple-bottom-line sustainability-based interpretative indicators. Variation among outcomes is explained with 54 similarly structured metrics of inputs, management approaches and enabling conditions. Using 61 initial fishery case studies drawn from industrial and developing countries around the world, we demonstrate the inferential importance of tracking economic and community outcomes, in addition to resource status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system. B lymphocytes in the cerebrospinal fluid (CSF) ...of patients with MS contribute to inflammation and secrete oligoclonal immunoglobulins
. Epstein-Barr virus (EBV) infection has been epidemiologically linked to MS, but its pathological role remains unclear
. Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and the central nervous system protein glial cell adhesion molecule (GlialCAM) and provide structural and in vivo functional evidence for its relevance. A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses. Sequence analysis, affinity measurements and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment enabled tracking of the development of the naive EBNA1-restricted antibody to a mature EBNA1-GlialCAM cross-reactive antibody. Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates disease in a mouse model of MS, and anti-EBNA1 and anti-GlialCAM antibodies are prevalent in patients with MS. Our results provide a mechanistic link for the association between MS and EBV and could guide the development of new MS therapies.
Dynamic adjustments to neuronal energy supply in response to synaptic activity are critical for neuronal function. Glial cells known as astrocytes have processes that ensheath most central synapses ...and express G-protein-coupled neurotransmitter receptors and transporters that respond to neuronal activity. Astrocytes also release substrates for neuronal oxidative phosphorylation and have processes that terminate on the surface of brain arterioles and can influence vascular smooth muscle tone and local blood flow. Membrane receptor or transporter-mediated effects of glutamate represent a convergence point of astrocyte influence on neuronal bioenergetics. Astrocytic glutamate uptake drives glycolysis and subsequent shuttling of lactate from astrocytes to neurons for oxidative metabolism. Astrocytes also convert synaptically reclaimed glutamate to glutamine, which is returned to neurons for glutamate salvage or oxidation. Finally, astrocytes store brain energy currency in the form of glycogen, which can be mobilized to produce lactate for neuronal oxidative phosphorylation in response to glutamatergic neurotransmission. These mechanisms couple synaptically driven astrocytic responses to glutamate with release of energy substrates back to neurons to match demand with supply. In addition, astrocytes directly influence the tone of penetrating brain arterioles in response to glutamatergic neurotransmission, coordinating dynamic regulation of local blood flow. We will describe the role of astrocytes in neurometabolic and neurovascular coupling in detail and discuss, in turn, how astrocyte dysfunction may contribute to neuronal bioenergetic deficit and neurodegeneration. Understanding the role of astrocytes as a hub for neurometabolic and neurovascular coupling mechanisms is a critical underpinning for therapeutic development in a broad range of neurodegenerative disorders characterized by chronic generalized brain ischemia and brain microvascular dysfunction.
Glutamate serves as the dominant central nervous system (CNS) excitatory neurotransmitter, in part by activating N -methyl-D-aspartate receptors (NMDARs). While the structure, function, and ...distribution of neuronal NMDARs have been extensively elucidated, NMDARs are also expressed across a wide spectrum of non-neuronal cells, including central and peripheral glial cells, endothelium, kidney, bone, pancreas, and others. These receptors are poorly understood compared to neuronal receptors, but there is a developing consensus that they have distinct structural and functional properties when activated by glutamate, NMDAR co-agonists, and in some cases by metabolites of tryptophan and methionine. It is also clear that non-neuronal NMDARs may participate in an array of physiological and pathophysiological processes, including but not limited to bone deposition, wound healing, insulin secretion, blood–brain barrier integrity, and myelination. These developing lines of evidence are stimulating exploration of non-neuronal NMDARs as a therapeutic target in several disorders.
Dynamic coupling of blood supply with energy demand is a natural brain property that requires signaling between synapses and endothelial cells. Our previous work showed that cortical arteriole lumen ...diameter is regulated by N-methyl-D-aspartate receptors (NMDARs) expressed by brain endothelial cells. The purpose of this study was to determine whether endothelial NMDARs (eNMDARs) regulate functional hyperemia in vivo. In response to whisker stimulation, regional cerebral blood flow (rCBF) and hemo-dynamic responses were assessed in barrel cortex of awake wild-type or eNMDAR loss-of-function mice using two-photon microscopy. Hyperemic enhancement of rCBF and vasodilation throughout the vascular network was observed in wild-type mice. eNMDAR loss of function reduced hyperemic responses in rCBF and plasma flux in individual vessels. Discovery of an endothelial receptor that regulates brain hyperemia provides insight into how neuronal activity couples with endothelial cells.
Three pillars of sustainability in fisheries Asche, Frank; Garlock, Taryn M.; Anderson, James L. ...
Proceedings of the National Academy of Sciences,
10/2018, Letnik:
115, Številka:
44
Journal Article
Recenzirano
Odprti dostop
Sustainability of global fisheries is a growing concern. The United Nations has identified three pillars of sustainability: economic development, social development, and environmental protection. The ...fisheries literature suggests that there are two key trade-offs among these pillars of sustainability. First, poor ecological health of a fishery reduces economic profits for fishers, and second, economic profitability of individual fishers undermines the social objectives of fishing communities. Although recent research has shown that management can reconcile ecological and economic objectives, there are lingering concerns about achieving positive social outcomes. We examined trade-offs among the three pillars of sustainability by analyzing the Fishery Performance Indicators, a unique dataset that scores 121 distinct fishery systems worldwide on 68 metrics categorized by social, economic, or ecological outcomes. For each of the 121 fishery systems, we averaged the outcome measures to create overall scores for economic, ecological, and social performance. We analyzed the scores and found that they were positively associated in the full sample. We divided the data into subsamples that correspond to fisheries management systems with three categories of access—open access, access rights, and harvest rights—and performed a similar analysis. Our results show that economic, social, and ecological objectives are at worst independent and are mutually reinforcing in both types of managed fisheries. The implication is that rights-based management systems should not be rejected on the basis of potentially negative social outcomes; instead, social considerations should be addressed in the design of these systems.
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