Rapid tonicity induced re-localisation of endogenous aquaporin 4 in primary rat astrocytes - a therapeutic target for cytotoxic brain oedema?

It is estimated that 69-75 million people worldwide will suffer a traumatic brain injury (TBI) or stroke each year. Brain oedema caused by TBI or following a stroke, together with other disorders of the brain cost Europe €770 billion in 2014. Aquaporins (AQP) are transmembrane water channels involved in many physiologies and are responsible for the maintenance of water homeostasis. They react rapidly to changes in osmolarity by transporting water through their highly selective central pore to maintain tonicity and aid in cell volume regulation. We have previously shown that recombinant AQP1-GFP trafficking occurs in a proteinkinase C-microtubule dependant manner in HEK-293 cells in response to hypotonicity. This trafficking mechanism is also reliant on the presence of calcium and its messenger-binding protein calmodulin and results in increased cell surface expression of AQP1 in a time-scale of ~30 seconds. There is currently very little research into the trafficking mechanisms of endogenous AQPs in primary cells. AQP4 is the most abundantly expressed AQP within the brain, it is localised to the astrocytic end-feet, in contact with the blood vessels at the blood-brain-barrier. In situations where the exquisitely-tuned osmotic balance is disturbed, high water permeability can become detrimental. AQP4-mediated water influx causes rapid brain swelling, resulting in death or long term brain damage. Previous research has shown that AQP4 knock-out mice were protected from the formation of cytotoxic brain oedema in a stroke model, highlighting AQP4 as a key drug target for this pathology. As there are currently no treatments available to restrict the flow of water through AQP4 as all known inhibitors are either cytotoxic or non-specific, controlling the mechanisms involved in the regulation of AQP4 in the brain could provide a therapeutic solution to such diseases. Using cell surface biontinylation of endogenous AQP4 in primary rat astrocytes followed by neutraavidin based ELISA we have shown that AQP4 cell surface localisation increases by 2.7 fold after 5 minutes hypotonic treatment at around 85 mOsm/kg H2O. We have also shown that this rapid relocalisation of AQP4 is regulated by PKA, calmodulin, extra-cellular calcium and actin. In summary we have shown that rapid translocation of endogenous AQP4 occurs in primary rat astrocytes in response to hypotonic stimuli; this mechanism is PKA, calcium, actin and calmodulin dependant. AQP4 has the potential to provide a treatment for the development of brain oedema.

Periphyton as an indicator of restoration in the Everglades

Periphyton communities dominate primary production in much of the Florida Everglades wetland and therefore contribute to soil production, ecosystem metabolism and secondary production as well as the composition of dependent communities. Decades of research in the Everglades have supported research findings from other wetland types that cumulatively show that periphyton communities respond very rapidly to alterations in the two dominant drivers of wetland structure and function—hydrology and water quality. Hydrology controls periphyton productivity and composition by regulating moisture availability, substrate types available for colonization and supply of nutrients. Nutrients, particularly the limiting nutrient in this system, phosphorus (P), control levels of production and community composition. Because periphyton communities are well-established to be related to hydrology and water quality, an indicator was developed based on three periphyton attributes: abundance, quality (i.e., nutrient content) and community composition. This assessment tool offers a qualitative assessment of ecosystem response to potential changes in management activities at a time scale appropriate for active management. An example is provided of how the indicator can be used to assess the current water quality and hydrological conditions from high-density spatial surveys. Detected patterns of deterioration align with expectations derived from model predictions and known sources of nutrients and unnatural hydrologic regimes. If employed adaptively in ecosystem management, this tool can be used to both detect and react to change before the system has been irreparably altered.

Impacts of hurricanes on surface water flow within a wetland

Between 2001 and 2005, seven category 3 or higher major hurricanes made landfall within the US. The hydrologic impacts of these distinct climatic phenomena frequently occurring in wetland watersheds, however, are not well understood. The focus of this study was to evaluate the impacts of hurricane wind and rainfall conditions on water velocity and water elevations within the study wetland, the Florida Everglades. Specifically water velocity data was measured near two tree islands (Gumbo Limbo (GL) and Satin Leaf (SL)) and wind speed, water elevation, and rainfall were obtained from nearby wind observation stations. During the direct impacts of the hurricanes (Hurricanes Katrina and Wilma), water speed, flow direction, and hydraulic gradients were altered, and the extent of variation was positively related to wind characteristics, with significant alterations in flow direction at depth during Hurricane Wilma due to higher wind speeds. After the direct impacts, the longer lasting effect of hurricanes (time scale of a few days) resulted in altered flow speeds that changed by 50% or less. These longer lasting changes in flow speeds may be due to the redistribution of emergent vegetation.

Sediment accretion and organic carbon burial relative to sea-level rise and storm events in two mangrove forests in Everglades National Park

The goal of this investigation was to examine how sediment accretion and organic carbon (OC) burial rates in mangrove forests respond to climate change. Specifically, will the accretion rates keep pace with sea-level rise, and what is the source and fate of OC in the system? Mass accumulation, accretion and OC burial rates were determined via 210Pb dating (i.e. 100 year time scale) on sediment cores collected from two mangrove forest sites within Everglades National Park, Florida (USA). Enhanced mass accumulation, accretion and OC burial rates were found in an upper layer that corresponded to a well-documented storm surge deposit. Accretion rates were 5.9 and 6.5 mm yr− 1 within the storm deposit compared to overall rates of 2.5 and 3.6 mm yr− 1. These rates were found to be matching or exceeding average sea-level rise reported for Key West, Florida. Organic carbon burial rates were 260 and 393 g m− 2 yr− 1 within the storm deposit compared to 151 and 168 g m− 2 yr− 1 overall burial rates. The overall rates are similar to global estimates for OC burial in marine wetlands. With tropical storms being a frequent occurrence in this region the resulting storm surge deposits are an important mechanism for maintaining both overall accretion and OC burial rates. Enhanced OC burial rates within the storm deposit could be due to an increase in productivity created from higher concentrations of phosphorus within storm-delivered sediments and/or from the deposition of allochthonous OC. Climate change-amplified storms and sea-level rise could damage mangrove forests, exposing previously buried OC to oxidation and contribute to increasing atmospheric CO2 concentrations. However, the processes described here provide a mechanism whereby oxidation of OC would be limited and the overall OC reservoir maintained within the mangrove forest sediments.

Lake metabolism and the diel oxygen technique: State of the science

Significant improvements have been made in estimating gross primary production (GPP), ecosystem respiration (R), and net ecosystem production (NEP) from diel, “free-water” changes in dissolved oxygen (DO). Here we evaluate some of the assumptions and uncertainties that are still embedded in the technique and provide guidelines on how to estimate reliable metabolic rates from high-frequency sonde data. True whole-system estimates are often not obtained because measurements reflect an unknown zone of influence which varies over space and time. A minimum logging frequency of 30 min was sufficient to capture metabolism at the daily time scale. Higher sampling frequencies capture additional pattern in the DO data, primarily related to physical mixing. Causes behind the often large daily variability are discussed and evaluated for an oligotrophic and a eutrophic lake. Despite a 3-fold higher day-to-day variability in absolute GPP rates in the eutrophic lake, both lakes required at least 3 sonde days per week for GPP estimates to be within 20% of the weekly average. A sensitivity analysis evaluated uncertainties associated with DO measurements, piston velocity (k), and the assumption that daytime R equals nighttime R. In low productivity lakes, uncertainty in DO measurements and piston velocity strongly impacts R but has no effect on GPP or NEP. Lack of accounting for higher R during the day underestimates R and GPP but has no effect on NEP. We finally provide suggestions for future research to improve the technique.

Sediment Accretion and Organic Carbon Burial Relative to Sea-Level Rise and Storm Events in Two Mangrove Forests in Everglades National Park

The goal of this investigation was to examine how sediment accretion and organic carbon (OC) burial rates in mangrove forests respond to climate change. Specifically, will the accretion rates keep pace with sea-level rise, and what is the source and fate of OC in the system? Mass accumulation, accretion and OC burial rates were determined via 210Pb dating (i.e. 100 year time scale) on sediment cores collected from two mangrove forest sites within Everglades National Park, Florida (USA). Enhanced mass accumulation, accretion and OC burial rates were found in an upper layer that corresponded to a well-documented storm surge deposit. Accretion rates were 5.9 and 6.5 mm yr− 1 within the storm deposit compared to overall rates of 2.5 and 3.6 mm yr− 1. These rates were found to be matching or exceeding average sea-level rise reported for Key West, Florida. Organic carbon burial rates were 260 and 393 g m− 2 yr− 1 within the storm deposit compared to 151 and 168 g m− 2 yr− 1 overall burial rates. The overall rates are similar to global estimates for OC burial in marine wetlands. With tropical storms being a frequent occurrence in this region the resulting storm surge deposits are an important mechanism for maintaining both overall accretion and OC burial rates. Enhanced OC burial rates within the storm deposit could be due to an increase in productivity created from higher concentrations of phosphorus within storm-delivered sediments and/or from the deposition of allochthonous OC. Climate change-amplified storms and sea-level rise could damage mangrove forests, exposing previously buried OC to oxidation and contribute to increasing atmospheric CO2 concentrations. However, the processes described here provide a mechanism whereby oxidation of OC would be limited and the overall OC reservoir maintained within the mangrove forest sediments.

Methane and stable isotope record of ice core EDML from Dronning Maud Land, Antarctica

Precise knowledge of the phase relationship between climate changes in the two hemispheres is a key for understanding the Earth's climate dynamics. For the last glacial period, ice core studies have revealed strong coupling of the largest millennial-scale warm events in Antarctica with the longest Dansgaard-Oeschger events in Greenland through the Atlantic meridional overturning circulation. It has been unclear, however, whether the shorter Dansgaard-Oeschger events have counterparts in the shorter and less prominent Antarctic temperature variations, and whether these events are linked by the same mechanism. Here we present a glacial climate record derived from an ice core from Dronning Maud Land, Antarctica, which represents South Atlantic climate at a resolution comparable with the Greenland ice core records. After methane synchronization with an ice core from North Greenland, the oxygen isotope record from the Dronning Maud Land ice core shows a one-to-one coupling between all Antarctic warm events and Greenland Dansgaard-Oeschger events by the bipolar seesaw. The amplitude of the Antarctic warm events is found to be linearly dependent on the duration of the concurrent stadial in the North, suggesting that they all result from a similar reduction in the meridional overturning circulation.

(Table S1) Uranium and Thorium isotopes and U/Th ages of IODP Exp310 cores from offshore Tahiti

The timing of sea-level change provides important constraints on the mechanisms driving Earth's climate between glacial and interglacial states. Fossil corals constrain the timing of past sea level by their suitability for dating and their growth position close to sea level. The coral-derived age for the last deglaciation is consistent with climate change forced by Northern Hemisphere summer insolation (NHI), but the timing of the penultimate deglaciation is more controversial. We found, by means of uranium/thorium dating of fossil corals, that sea level during the penultimate deglaciation had risen to ~85 meters below the present sea level by 137,000 years ago, and that it fluctuated on a millennial time scale during deglaciation. This indicates that the penultimate deglaciation occurred earlier with respect to NHI than the last deglacial, beginning when NHI was at a minimum.

Dinocyst assemblages of site HM52-43

Past sea-surface conditions over the northern North Atlantic during the last glacial maximum were examined from the study of 61 deep-sea cores. The last glacial maximum time slice studied here corresponds to an interval between Heinrich layers H2 and H1, and spanning about 20-16 ka on a 14C time scale. Transfer functions based on dinocyst assemblages were used to reconstruct sea-surface temperature, salinity, and sea-ice cover. The results illustrate extensive sea-ice cover along the eastern Canadian margins and sea-ice spreading, only during winter, over most of the northern North Atlantic. On the whole, much colder winter prevailed, despite relatively mild conditions in August (10-15°C at most offshore sites), thus suggesting a larger seasonal contrast of temperatures than today. Lower salinity than at present is reconstructed, especially along the eastern Canadian and Scandinavian margins, likely because of meltwater supply from the surrounding ice sheets. These reconstructions contrast with those established by CLIMAP on the basis of planktonic foraminifera. These differences are discussed with reference to the stratigraphical frame of the last glacial maximum, which was not the coldest phase of the last glacial stage. The respective significance of dinocyst and foraminifer records is also examined in terms of the thermohaline characteristics of surface waters and the vertical structure of upper water masses, which was apparently much more stratified than at present in the northern North Atlantic, thus preventing deep-water formation.

Stochastically forced dislocation density distribution in plastic deformation

The dynamical evolution of dislocations in plastically deformed metals is controlled by both deterministic factors arising out of applied loads and stochastic effects appearing due to fluctuations of internal stress. Such type of stochastic dislocation processes and the associated spatially inhomogeneous modes lead to randomness in the observed deformation structure. Previous studies have analyzed the role of randomness in such textural evolution but none of these models have considered the impact of a finite decay time (all previous models assumed instantaneous relaxation which is "unphysical") of the stochastic perturbations in the overall dynamics of the system. The present article bridges this knowledge gap by introducing a colored noise in the form of an Ornstein-Uhlenbeck noise in the analysis of a class of linear and nonlinear Wiener and Ornstein-Uhlenbeck processes that these structural dislocation dynamics could be mapped on to. Based on an analysis of the relevant Fokker-Planck model, our results show that linear Wiener processes remain unaffected by the second time scale in the problem but all nonlinear processes, both Wiener type and Ornstein-Uhlenbeck type, scale as a function of the noise decay time τ. The results are expected to ramify existing experimental observations and inspire new numerical and laboratory tests to gain further insight into the competition between deterministic and random effects in modeling plastically deformed samples.

Data-Driven Motion Detection and Characterization in PET Brain Scans Using List Mode

Head motion during a Positron Emission Tomography (PET) brain scan can considerably degrade image quality. External motion-tracking devices have proven successful in minimizing this effect, but the associated time, maintenance, and workflow changes inhibit their widespread clinical use. List-mode PET acquisition allows for the retroactive analysis of coincidence events on any time scale throughout a scan, and therefore potentially offers a data-driven motion detection and characterization technique. An algorithm was developed to parse list-mode data, divide the full acquisition into short scan intervals, and calculate the line-of-response (LOR) midpoint average for each interval. These LOR midpoint averages, known as “radioactivity centroids,” were presumed to represent the center of the radioactivity distribution in the scanner, and it was thought that changes in this metric over time would correspond to intra-scan motion.

Several scans were taken of the 3D Hoffman brain phantom on a GE Discovery IQ PET/CT scanner to test the ability of the radioactivity to indicate intra-scan motion. Each scan incrementally surveyed motion in a different degree of freedom (2 translational and 2 rotational). The radioactivity centroids calculated from these scans correlated linearly to phantom positions/orientations. Centroid measurements over 1-second intervals performed on scans with ~1mCi of activity in the center of the field of view had standard deviations of 0.026 cm in the x- and y-dimensions and 0.020 cm in the z-dimension, which demonstrates high precision and repeatability in this metric. Radioactivity centroids are thus shown to successfully represent discrete motions on the submillimeter scale. It is also shown that while the radioactivity centroid can precisely indicate the amount of motion during an acquisition, it fails to distinguish what type of motion occurred.

Calcium/Calmodulin-Dependent Protein Kinase II Serves as a Biochemical Integrator of Calcium Signals for the Induction of Synaptic Plasticity

Repetitive Ca2+ transients in dendritic spines induce various forms of synaptic plasticity by transmitting information encoded in their frequency and amplitude. CaMKII plays a critical role in decoding these Ca2+ signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca2+ decoding in spines remain elusive. Here, I measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each repetitive Ca2+ elevations, CaMKII activity increased in a stepwise manner. This signal integration, at the time scale of seconds, critically depended on Thr286 phosphorylation. In the absence of Thr286 phosphorylation, only by increasing the frequency of repetitive Ca2+ elevations could high peak CaMKII activity or plasticity be induced. In addition, I measured the association between CaMKII and Ca2+/CaM during spine plasticity induction. Unlike CaMKII activity, association of Ca2+/CaM to CaMKII plateaued at the first Ca2+ elevation event. This result indicated that integration of Ca2+ signals was initiated by the binding of Ca2+/CaM and amplified by the subsequent increases in Thr286-phosphorylated form of CaMKII. Together, these findings demonstrate that CaMKII functions as a leaky integrator of repetitive Ca2+ signals during the induction of synaptic plasticity, and that Thr286 phosphorylation is critical for defining the frequencies of such integration.

Barite accumulation rates throughout Pliocene-Pleistocene in Eastern Equatorial Pacific at ODP Site 138-849

Export production is an important component of the carbon cycle, modulating the climate system by transferring CO2 from the atmosphere to the deep ocean via the biological pump. Here we use barite accumulation rates to reconstruct export production in the eastern equatorial Pacific over the past 4.3 Ma. We find that export production fluctuated considerably on multiple time scales. Export production was on average higher (51 g C/m**2/yr) during the Pliocene than the Pleistocene (40 g C/m**2/yr), decreasing between 3 and 1 Ma (from more than 60 to 20 g C/m**2/yr) followed by an increase over the last million years. These trends likely reflect basin-scale changes in nutrient inventory and ocean circulation. Our record reveals decoupling between export production and temperatures on these long (million years) time scale. On orbital time scales, export production was generally higher during cold periods (glacial maxima) between 4.3 and 1.1 Ma. This could be due to stronger wind stress and higher upwelling rates during glacial periods. A shift in the timing of maximum export production to deglaciations is seen in the last ~1.1 million years. Results from this study suggest that, in the eastern equatorial Pacific, mechanisms that affect nutrient supply and/or ecosystem structure and in turn carbon export on orbital time scales differ from those operating on longer time scales and that processes linking export production and climate-modulated oceanic conditions changed about 1.1 million years ago. These observations should be accounted for in climate models to ensure better predictions of future climate change.