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Across western North America (WNA), 20th-21st century anthropogenic warming has increased the prevalence and severity of concurrent drought and heat events, also termed hot droughts. However, the lack of independent spatial reconstructions of both soil moisture and temperature limits the potential to identify these events in the past and to place them in a long-term context. We develop the Western North American Temperature Atlas (WNATA), a data-independent 0.5° gridded reconstruction of summer maximum temperatures back to the 16th century. Our evaluation of the WNATA with existing hydroclimate reconstructions reveals an increasing association between maximum temperature and drought severity in recent decades, relative to the past five centuries. The synthesis of these paleo-reconstructions indicates that the amplification of the modern WNA megadrought by increased temperatures and the frequency and spatial extent of compound hot and dry conditions in the 21st century are likely unprecedented since at least the 16th century.
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Arid and semi-arid regions of the world are particularly vulnerable to greenhouse gas-driven hydroclimate change. Climate models are our primary tool for projecting the future hydroclimate that society in these regions must adapt to, but here, we present a concerning discrepancy between observed and model-based historical hydroclimate trends. Over the arid/semi-arid regions of the world, the predominant signal in all model simulations is an increase in atmospheric water vapor, on average, over the last four decades, in association with the increased water vapor-holding capacity of a warmer atmosphere. In observations, this increase in atmospheric water vapor has not happened, suggesting that the availability of moisture to satisfy the increased atmospheric demand is lower in reality than in models in arid/semi-arid regions. This discrepancy is most clear in locations that are arid/semi-arid year round, but it is also apparent in more humid regions during the most arid months of the year. It indicates a major gap in our understanding and modeling capabilities which could have severe implications for hydroclimate projections, including fire hazard, moving forward.
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Kainate receptors (KARs) are key regulators of neuronal excitability and synaptic transmission. KAR surface expression is tightly controlled in part by post-translational modifications (PTMs) of the GluK2 subunit. We have shown previously that agonist activation of GluK2-containing KARs leads to phosphorylation of GluK2 at S868, which promotes subsequent SUMOylation at K886 and receptor endocytosis. Furthermore, GluK2 has been shown to be palmitoylated. However, how the interplay between palmitoylation, phosphorylation and SUMOylation orchestrate KAR trafficking remains unclear. Here, we used a library of site-specific GluK2 mutants to investigate the interrelationship between GluK2 PTMs, and their impact on KAR surface expression. We show that GluK2 is basally palmitoylated and that this is decreased by kainate (KA) stimulation. Moreover, a non-palmitoylatable GluK2 mutant (C858/C871A) shows enhanced S868 phosphorylation and K886 SUMOylation under basal conditions and is insensitive to KA-induced internalisation. These results indicate that GluK2 palmitoylation contributes to stabilising KAR surface expression and that dynamic depalmitoylation promotes downstream phosphorylation and SUMOylation to mediate activity-dependent KAR endocytosis.
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Most current climate models predict that the equatorial Pacific will evolve under greenhouse gas-induced warming to a more El Niño-like state over the next several decades, with a reduced zonal sea surface temperature gradient and weakened atmospheric Walker circulation. Yet, observations over the last 50 y show the opposite trend, toward a more La Niña-like state. Recent research provides evidence that the discrepancy cannot be dismissed as due to internal variability but rather that the models are incorrectly simulating the equatorial Pacific response to greenhouse gas warming. This implies that projections of regional tropical cyclone activity may be incorrect as well, perhaps even in the direction of change, in ways that can be understood by analogy to historical El Niño and La Niña events: North Pacific tropical cyclone projections will be too active, North Atlantic ones not active enough, for example. Other perils, including severe convective storms and droughts, will also be projected erroneously. While it can be argued that these errors are transient, such that the models' responses to greenhouse gases may be correct in equilibrium, the transient response is relevant for climate adaptation in the next several decades. Given the urgency of understanding regional patterns of climate risk in the near term, it would be desirable to develop projections that represent a broader range of possible future tropical Pacific warming scenarios-including some in which recent historical trends continue-even if such projections cannot currently be produced using existing coupled earth system models.
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Recent record rainfall and flood events have prompted increased attention to flood impacts on human systems. Information regarding flood effects on food security is of particular importance for humanitarian organizations and is especially valuable across Africa's rural areas that contribute to regional food supplies. We quantitatively evaluate where and to what extent flooding impacts food security across Africa, using a Granger causality analysis and panel modeling approaches. Within our modeled areas, we find that â¼12% of the people that experienced food insecurity from 2009 to 2020 had their food security status affected by flooding. Furthermore, flooding and its associated meteorological conditions can simultaneously degrade food security locally while enhancing it at regional spatial scales, leading to large variations in overall food security outcomes. Dedicated data collection at the intersection of flood events and associated food security measures across different spatial and temporal scales are required to better characterize the extent of flood impact and inform preparedness, response, and recovery needs.
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Inundaciones , Abastecimiento de Alimentos , África , Recolección de Datos , Seguridad Alimentaria , HumanosRESUMEN
It is well established that long-term depression (LTD) can be initiated by either NMDA or mGluR activation. Here we report that sustained activation of GluK2 subunit-containing kainate receptors (KARs) leads to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) endocytosis and induces LTD of AMPARs (KAR-LTDAMPAR) in hippocampal neurons. The KAR-evoked loss of surface AMPARs is blocked by the ionotropic KAR inhibitor UBP 310 indicating that KAR-LTDAMPAR requires KAR channel activity. Interestingly, however, blockade of PKC or PKA also reduces GluA2 surface expression and occludes the effect of KAR activation. In acute hippocampal slices, kainate application caused a significant loss of GluA2-containing AMPARs from synapses and long-lasting depression of AMPAR excitatory postsynaptic currents in CA1. These data, together with our previously reported KAR-LTPAMPAR, demonstrate that KARs can bidirectionally regulate synaptic AMPARs and synaptic plasticity via different signaling pathways.
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Biophysical vegetation responses to elevated atmospheric carbon dioxide (CO2) affect regional hydroclimate through two competing mechanisms. Higher CO2 increases leaf area (LAI), thereby increasing transpiration and water losses. Simultaneously, elevated CO2 reduces stomatal conductance and transpiration, thereby increasing rootzone soil moisture. Which mechanism dominates in the future is highly uncertain, partly because these two processes are difficult to explicitly separate within dynamic vegetation models. We address this challenge by using the GISS ModelE global climate model to conduct a novel set of idealized 2×CO2 sensitivity experiments to: evaluate the total vegetation biophysical contribution to regional climate change under high CO2; and quantify the separate contributions of enhanced LAI and reduced stomatal conductance to regional hydroclimate responses. We find that increased LAI exacerbates soil moisture deficits across the sub-tropics and more water-limited regions, but also attenuates warming by â¼0.5-1°C in the US Southwest, Central Asia, Southeast Asia, and northern South America. Reduced stomatal conductance effects contribute â¼1°C of summertime warming. For some regions, enhanced LAI and reduced stomatal conductance produce nonlinear and either competing or mutually amplifying hydroclimate responses. In northeastern Australia, these effects combine to exacerbate radiation-forced warming and contribute to year-round water limitation. Conversely, at higher latitudes these combined effects result in less warming than would otherwise be predicted due to nonlinear responses. These results highlight substantial regional variation in CO2-driven vegetation responses and the importance of improving model representations of these processes to better quantify regional hydroclimate impacts.
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The reactivity of platelets, which play a key role in the pathogenesis of atherothrombosis, is tightly regulated. The integral membrane protein tetherin/bone marrow stromal antigen-2 (BST-2) regulates membrane organization, altering both lipid and protein distribution within the plasma membrane. Because membrane microdomains have an established role in platelet receptor biology, we sought to characterize the physiological relevance of tetherin/BST-2 in those cells. To characterize the potential importance of tetherin/BST-2 to platelet function, we used tetherin/BST-2-/- murine platelets. In the mice, we found enhanced function and signaling downstream of a subset of membrane microdomain-expressing receptors, including the P2Y12, TP thromboxane, thrombin, and GPVI receptors. Preliminary studies in humans have revealed that treatment with interferon-α (IFN-α), which upregulates platelet tetherin/BST-2 expression, also reduces adenosine diphosphate-stimulated platelet receptor function and reactivity. A more comprehensive understanding of how tetherin/BST-2 negatively regulates receptor function was provided in cell line experiments, where we focused on the therapeutically relevant P2Y12 receptor (P2Y12R). Tetherin/BST-2 expression reduced both P2Y12R activation and trafficking, which was accompanied by reduced receptor lateral mobility specifically within membrane microdomains. In fluorescence lifetime imaging-Förster resonance energy transfer (FLIM-FRET)-based experiments, agonist stimulation reduced basal association between P2Y12R and tetherin/BST-2. Notably, the glycosylphosphatidylinositol (GPI) anchor of tetherin/BST-2 was required for both receptor interaction and observed functional effects. In summary, we established, for the first time, a fundamental role of the ubiquitously expressed protein tetherin/BST-2 in negatively regulating membrane microdomain-expressed platelet receptor function.
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Antígenos CD , Antígeno 2 del Estroma de la Médula Ósea , Animales , Antígenos CD/genética , Plaquetas , Línea Celular , Proteínas Ligadas a GPI/genética , RatonesRESUMEN
Epilepsy is caused when rhythmic neuronal network activity escapes normal control mechanisms, resulting in seizures. There is an extensive and growing body of evidence that the onset and maintenance of epilepsy involves alterations in the trafficking, synaptic surface expression and signalling of kainate and AMPA receptors (KARs and AMPARs). The KAR subunit GluK2 and AMPAR subunit GluA2 are key determinants of the properties of their respective assembled receptors. Both subunits are subject to extensive protein interactions, RNA editing and post-translational modifications. In this review we focus on the cell biology of GluK2-containing KARs and GluA2-containing AMPARs and outline how their regulation and dysregulation is implicated in, and affected by, seizure activity. Further, we discuss role of KARs in regulating AMPAR surface expression and plasticity, and the relevance of this to epilepsy. This article is part of the special issue on 'Glutamate Receptors - Kainate receptors'.
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Encéfalo/metabolismo , Epilepsia/metabolismo , Neuronas/metabolismo , Receptores AMPA/metabolismo , Receptores de Ácido Kaínico/metabolismo , Transducción de Señal/fisiología , Animales , Humanos , Sinapsis/metabolismoRESUMEN
Conflict, drought and locusts are leading concerns for African food security but the relative importance and spatiotemporal scale of crises resulting from each hazard is poorly characterized. Here we use continuous, subnational data to demonstrate that the rise of food insecurity across sub-Saharan Africa that began in 2014 is attributable to an increase in violent conflict, particularly in South Sudan and Nigeria. Although drought remains a leading trigger of food crises, the prevalence of drought-related crises did not increase from 2009 to 2018. When exposed to drought, pastoralists experienced more widespread, severe and long-lasting food crises than people living in agricultural zones. Food insecurity remained elevated in pastoral regions for 2 years following a drought, while agricultural regions returned to pre-drought food-security levels in ~12 months. The few confirmed famines during the 2009-2018 period coincided with both conflict and drought, while locusts had little effect on food security during this period.
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SUMOylation is a post-translational modification that regulates protein signalling and complex formation by adjusting the conformation or protein-protein interactions of the substrate protein. There is a compelling and rapidly expanding body of evidence that, in addition to SUMOylation of nuclear proteins, SUMOylation of extranuclear proteins contributes to the control of neuronal development, neuronal stress responses and synaptic transmission and plasticity. In this brief review we provide an update of recent developments in the identification of synaptic and synapse-associated SUMO target proteins and discuss the cell biological and functional implications of these discoveries.
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Sumoilación/fisiología , Sinapsis/metabolismo , Animales , HumanosRESUMEN
Neurons are highly polarised, complex and incredibly energy intensive cells, and their demand for ATP during neuronal transmission is primarily met by oxidative phosphorylation by mitochondria. Thus, maintaining the health and efficient function of mitochondria is vital for neuronal integrity, viability and synaptic activity. Mitochondria do not exist in isolation, but constantly undergo cycles of fusion and fission, and are actively transported around the neuron to sites of high energy demand. Intriguingly, axonal and dendritic mitochondria exhibit different morphologies. In axons mitochondria are small and sparse whereas in dendrites they are larger and more densely packed. The transport mechanisms and mitochondrial dynamics that underlie these differences, and their functional implications, have been the focus of concerted investigation. Moreover, it is now clear that deficiencies in mitochondrial dynamics can be a primary factor in many neurodegenerative diseases. Here, we review the role that mitochondrial dynamics play in neuronal function, how these processes support synaptic transmission and how mitochondrial dysfunction is implicated in neurodegenerative disease.
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Multidecadal "megadroughts" were a notable feature of the climate of the American Southwest over the Common era, yet we still lack a comprehensive theory for what caused these megadroughts and why they curiously only occurred before about 1600 CE. Here, we use the Paleo Hydrodynamics Data Assimilation product, in conjunction with radiative forcing estimates, to demonstrate that megadroughts in the American Southwest were driven by unusually frequent and cold central tropical Pacific sea surface temperature (SST) excursions in conjunction with anomalously warm Atlantic SSTs and a locally positive radiative forcing. This assessment of past megadroughts provides the first comprehensive theory for the causes of megadroughts and their clustering particularly during the Medieval era. This work also provides the first paleoclimatic support for the prediction that the risk of American Southwest megadroughts will markedly increase with global warming.
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The mitochondrial outer membrane protein Mitochondrial Fission Factor (Mff) plays a key role in both physiological and pathological fission. It is well established that at stressed or functionally impaired mitochondria, PINK1 recruits the ubiquitin ligase Parkin which ubiquitinates Mff and other mitochondrial outer membrane proteins to facilitate the removal of defective mitochondria and maintain the integrity of the mitochondrial network. Here we show that, in addition to this clearance pathway, Parkin also ubiquitinates Mff in a PINK1-dependent manner under non-stressed conditions to regulate constitutive Mff turnover. We further show that removing Parkin via shRNA-mediated knockdown does not completely prevent Mff ubiquitination under these conditions, indicating that at least one other ubiquitin ligase contributes to Mff proteostasis. These data suggest that that Parkin plays a role in physiological maintenance of mitochondrial membrane protein composition in unstressed cells through constitutive low-level activation.
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Proteínas de la Membrana/metabolismo , Dinámicas Mitocondriales , Proteínas Mitocondriales/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Técnicas de Cultivo de Célula , Técnicas de Silenciamiento del Gen , Células HEK293 , Humanos , Lisosomas/metabolismo , Proteínas de la Membrana/genética , Dinámicas Mitocondriales/genética , Proteínas Mitocondriales/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Proteolisis , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , UbiquitinaciónRESUMEN
Much of the eastern United States (US) experienced increased precipitation over the 20th century. Characterizing these trends and their causes is critical for assessing future hydroclimate risks. Here, US precipitation trends are analyzed during 1895-2016, revealing that fall precipitation in the southeastern region north of the Gulf of Mexico (SE-Gulf) increased by nearly 40%, primarily increasing after the mid-1900s. As fall is the climatological dry season in the SE-Gulf and precipitation in other seasons changed insignificantly, the seasonal precipitation cycle diminished substantially. The increase in SE-Gulf fall precipitation was caused by increased southerly moisture transport from the Gulf of Mexico, which was almost entirely driven by stronger winds associated with enhanced anticyclonic circulation west of the North Atlantic Subtropical High (NASH) and not by increases in specific humidity. Atmospheric models forced by observed SSTs and fully-coupled models forced by historical anthropogenic forcing do not robustly simulate 20th-century fall wetting in the SE-Gulf. SST-forced atmospheric models do simulate an intensified anticyclonic low-level circulation around the NASH, but the modeled intensification occurred farther west than observed. CMIP5 analyses suggest an increased likelihood of positive SE-Gulf fall precipitation trends given historical and future GHG forcing. Nevertheless, individual model simulations (both SST-forced and fully-coupled) only very rarely produce the observed magnitude of the SE-Gulf fall precipitation trend. Further research into model representation of the western ridge of the fall NASH is needed, which will help us better predict whether 20th-century increases in SE-Gulf fall precipitation will persist into the future.
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The tree-ring-based North American Drought Atlas (NADA), Monsoon Asia Drought Atlas (MADA), and Old World Drought Atlas (OWDA) collectively yield a near-hemispheric gridded reconstruction of hydroclimate variability over the last millennium. To test the robustness of the large-scale representation of hydroclimate variability across the drought atlases, the joint expression of seasonal climate variability and teleconnections in the NADA, MADA, and OWDA are compared against two global, observation-based PDSI products. Predominantly positive (negative) correlations are determined between seasonal precipitation (surface air temperature) and collocated tree-ring-based PDSI, with average Pearson's correlation coefficients increasing in magnitude from boreal winter to summer. For precipitation, these correlations tend to be stronger in the boreal winter and summer when calculated for the observed PDSI record, while remaining similar for temperature. Notwithstanding these differences, the drought atlases robustly express teleconnection patterns associated with the El Niño-Southern Oscillation (ENSO), North Atlantic Oscillation (NAO), Pacific Decadal Oscillation (PDO), and Atlantic Multidecadal Oscillation (AMO). These expressions exist in the drought atlas estimates of boreal summer PDSI despite the fact that these modes of climate variability are dominant in boreal winter, with the exception of the Atlantic Multidecadal Oscillation. ENSO and NAO teleconnection patterns in the drought atlases are particularly consistent with their well-known dominant expressions in boreal winter and over the OWDA domain, respectively. Collectively, our findings confirm that the joint Northern Hemisphere drought atlases robustly reflect large-scale patterns of hydroclimate variability on seasonal to multidecadal timescales over the 20th century and are likely to provide similarly robust estimates of hydroclimate variability prior to the existence of widespread instrumental data.
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The fall 2016 drought in the southeastern United States (SE US) appeared exceptional based on its widespread impacts, but the current monitoring framework that only extends from 1979-present does not readily facilitate evaluation of soil-moisture anomalies in a centennial context. A new method to extend monthly gridded soil-moisture estimates back to 1895 is developed, indicating that since 1895, October-November 2016 soil moisture (0-200 cm) in the SE US was likely the second lowest on record, behind 1954. This severe drought developed rapidly and was brought on by low September-November precipitation and record-high September-November daily maximum temperatures (Tmax). Record Tmax drove record-high atmospheric moisture demand, accounting for 28% of the October-November 2016 soil-moisture anomaly. Drought and heat in fall 2016 contrasted with 20th-century wetting and cooling in the region, but resembled conditions more common from 1895-1956. Dynamically, the exceptional drying in fall 2016 was driven by anomalous ridging over the central United States that reduced south-southwesterly moisture transports into the SE US by approximately 75%. These circulation anomalies were likely promoted by a moderate La Niña and warmth in the tropical Atlantic, but these processes accounted for very little of the SE US drying in fall 2016, implying a large role for internal atmospheric variability. The extended analysis back to 1895 indicates that SE US droughts as strong as the 2016 event are more likely than indicated from a shorter 60-year perspective, and continued multi-decadal swings in precipitation may combine with future warming to further enhance the likelihood of such events.
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Climate models project significant twenty-first-century declines in water availability over the American West from anthropogenic warming. However, the physical mechanisms underpinning this response are poorly characterized, as are the uncertainties from vegetation's modulation of evaporative losses. To understand the drivers and uncertainties of future hydroclimate in the American West, a 35-member single model ensemble is used to examine the response of summer soil moisture and runoff to anthropogenic forcing. Widespread dry season soil moisture declines occur across the region despite increases in total water-year precipitation and ubiquitous increases in plant water-use efficiency. These modeled soil moisture declines are initially forced by significant snowpack losses that directly diminish summer soil water, even in regions where water-year precipitation increases. When snowpack priming is coupled with a warming- and CO2-induced shift in phenology and increased primary production, widespread increases in leaf area further reduces summer soil moisture and runoff by outpacing decreased stomatal conductance from high CO2. The net effects lead to the cooccurrence of both a "greener" and "drier" future across the western United States. Because simulated vegetation exerts a large influence on predicted changes in water availability in the American West, these findings highlight the importance of reducing the substantial uncertainties in the ecological processes increasingly incorporated into numerical Earth system models.
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We explore use of the familiar tercile framework of seasonal forecasting for the characterization of 21st-century precipitation projections over North America. Consistent with direct analyses of modeled precipitation change, in a superensemble of CMIP5 simulations an unambiguous pattern of shifted tercile population statistics develops as the globe warms. Expressed categorically, frequencies for the low (i.e., dry) tercile increase in the southwestern United States and southward into Mexico and decrease across the northern tier of North America, while counts for the high tercile shift in the opposite sense. We show that as the 21st-century proceeds, changes become statistically significant over wide regions in the pointwise sense, and also when considered as projections on model-specific climate change "fingerprints". Background noise in the superensemble, against which significance is established, comprises both structural model uncertainty and natural climate variability. The robustness of these findings makes a compelling case for long-range planning for a dryer future in the American Southwest and southward, and wetter one to the north and especially northeast, while communication is facilitated by widespread user familiarity with the tercile format.
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Climate model projections suggest widespread drying in the Mediterranean Basin and wetting in Fennoscandia in the coming decades largely as a consequence of greenhouse gas forcing of climate. To place these and other "Old World" climate projections into historical perspective based on more complete estimates of natural hydroclimatic variability, we have developed the "Old World Drought Atlas" (OWDA), a set of year-to-year maps of tree-ring reconstructed summer wetness and dryness over Europe and the Mediterranean Basin during the Common Era. The OWDA matches historical accounts of severe drought and wetness with a spatial completeness not previously available. In addition, megadroughts reconstructed over north-central Europe in the 11th and mid-15th centuries reinforce other evidence from North America and Asia that droughts were more severe, extensive, and prolonged over Northern Hemisphere land areas before the 20th century, with an inadequate understanding of their causes. The OWDA provides new data to determine the causes of Old World drought and wetness and attribute past climate variability to forced and/or internal variability.