Ion channel function of aquaporin-1 natively expressed in choroid plexus

Aquaporins are known as water channels; however, an additional ion channel function has been observed for several including aquaporin-1 (AQP1). Using primary cultures of rat choroid plexus, a brain tissue that secretes CSF and abundantly expresses AQP1, we confirmed the ion channel function of AQP1 and assessed its functional relevance. The cGMP-gated cationic conductance associated with AQP1 is activated by an endogenous receptor guanylate cyclase for atrial natriuretic peptide (ANP). Fluid transport assays with confluent polarized choroid plexus cultures showed that AQP1 current activation by 4.5 μM ANP decreases the normal basal-to-apical fluid transport in the choroid plexus; conversely, AQP1 block with 500 μM Cd²⁺ restores fluid transport. The cGMP-gated conductance in the choroid plexus is lost with targeted knockdown of AQP1 by small interfering RNA (siRNA), as confirmed by immunocytochemistry and whole-cell patch electrophysiology of transiently transfected cells identified by enhanced green fluorescent protein. The properties of the current (permeability to Na⁺, K⁺, TEA⁺, and Cs⁺; voltage insensitivity; and dependence on cGMP) matched properties characterized previously in AQP1-expressing oocytes. Background K⁺ and Cl⁻ currents in the choroid plexus were dissected from AQP1 currents using Cs-methanesulfonate recording salines; the background currents recorded in physiological salines were not affected by AQP1–siRNA treatment. These results confirm that AQP1 can function as both a water channel and a gated ion channel. The conclusion that the AQP1-associated cation current contributes to modulating CSF production resolves a lingering concern as to whether an aquaporin ionic conductance can have a physiologically relevant function.Daniela Boassa, W. Daniel Stamer and Andrea J. Yoo

Climate change and ocean acidification impacts on lower trophic levels and the export of organic carbon to the deep ocean

Most future projections forecast significant and ongoing climate change during the 21st century, but with the severity of impacts dependent on efforts to restrain or reorganise human activity to limit carbon dioxide (CO2) emissions. A major sink for atmospheric CO2, and a key source of biological resources, the World Ocean is widely anticipated to undergo profound physical and – via ocean acidification – chemical changes as direct and indirect results of these emissions. Given strong biophysical coupling, the marine biota is also expected to experience strong changes in response to this anthropogenic forcing. Here we examine the large-scale response of ocean biogeochemistry to climate and acidification impacts during the 21st century for Representative Concentration Pathways (RCPs) 2.6 and 8.5 using an intermediate complexity global ecosystem model, MEDUSA-2.0. The primary impact of future change lies in stratification-led declines in the availability of key nutrients in surface waters, which in turn leads to a global decrease (1990s vs. 2090s) in ocean productivity (?6.3%). This impact has knock-on consequences for the abundance of the low trophic level biogeochemical actors modelled by MEDUSA-2.0 (?5.8%), and these would be expected to similarly impact higher trophic level elements such as fisheries. Related impacts are found in the flux of organic material to seafloor communities (?40.7% at 1000 m), and in the volume of ocean suboxic zones (+12.5%). A sensitivity analysis removing an acidification feedback on calcification finds that change in this process significantly impacts benthic communities, suggesting that a~better understanding of the OA-sensitivity of calcifying organisms, and their role in ballasting sinking organic carbon, may significantly improve forecasting of these ecosystems. For all processes, there is geographical variability in change – for instance, productivity declines ?21% in the Atlantic and increases +59% in the Arctic – and changes are much more pronounced under RCP 8.5 than the RCP 2.6 scenario

Compartmentalized PDE4A5 signaling impairs hippocampal synaptic plasticity and long-term memory

Alterations in cAMP signaling are thought to contribute to neurocognitive and neuropsychiatric disorders. Members of the cAMP-specific phosphodiesterase 4 (PDE4) family, which contains >25 different isoforms, play a key role in determining spatial cAMP degradation so as to orchestrate compartmentalized cAMP signaling in cells. Each isoform binds to a different set of protein complexes through its unique N-terminal domain, thereby leading to targeted degradation of cAMP in specific intracellular compartments. However, the functional role of specific compartmentalized PDE4 isoforms has not been examined in vivo. Here, we show that increasing protein levels of the PDE4A5 isoform in mouse hippocampal excitatory neurons impairs a long-lasting form of hippocampal synaptic plasticity and attenuates hippocampus-dependent long-term memories without affecting anxiety. In contrast, viral expression of a truncated version of PDE4A5, which lacks the unique N-terminal targeting domain, does not affect long-term memory. Further, overexpression of the PDE4A1 isoform, which targets a different subset of signalosomes, leaves memory undisturbed. Fluorescence resonance energy transfer sensor-based cAMP measurements reveal that the full-length PDE4A5, in contrast to the truncated form, hampers forskolin-mediated increases in neuronal cAMP levels. Our study indicates that the unique N-terminal localization domain of PDE4A5 is essential for the targeting of specific cAMP-dependent signaling underlying synaptic plasticity and memory. The development of compounds to disrupt the compartmentalization of individual PDE4 isoforms by targeting their unique N-terminal domains may provide a fruitful approach to prevent cognitive deficits in neuropsychiatric and neurocognitive disorders that are associated with alterations in cAMP signaling

EcoGEnIE 1.0: plankton ecology in the cGEnIE Earth system model

We present an extension to the carbon-centric Grid Enabled Integrated Earth system model (cGEnIE) that explicitly accounts for the growth and interaction of an arbitrary number of plankton species. The new package (ECOGEM) replaces the implicit, flux-based parameterisation of the plankton community currently employed, with explicitly resolved plankton populations and ecological dynamics. In ECOGEM, any number of plankton species, with ecophysiological traits (e.g. growth and grazing rates) assigned according to organism size and functional group (e.g. phytoplankton and zooplankton) can be incorporated at runtime. We illustrate the capability of the marine ecology enabled Earth system model (EcoGEnIE) by comparing results from one configuration of ECOGEM (with eight generic phytoplankton and zooplankton size classes) to climatological and seasonal observations. We find that the new ecological components of the model show reasonable agreement with both global-scale climatological and local-scale seasonal data. We also compare EcoGEnIE results to the existing biogeochemical incarnation of cGEnIE. We find that the resulting global-scale distributions of phosphate, iron, dissolved inorganic carbon, alkalinity, and oxygen are similar for both iterations of the model. A slight deterioration in some fields in EcoGEnIE (relative to the data) is observed, although we make no attempt to re-tune the overall marine cycling of carbon and nutrients here. The increased capabilities of EcoGEnIE in this regard will enable future exploration of the ecological community on much longer timescales than have previously been examined in global ocean ecosystem models and particularly for past climates and global biogeochemical cycles

Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia

Oligodendrocytes are critical for the development of the plasma membrane and cytoskeleton of the axon. In this paper, we show that fast axonal transport is also dependent on the oligodendrocyte. Using a mouse model of hereditary spastic paraplegia type 2 due to a null mutation of the myelin Plp gene, we find a progressive impairment in fast retrograde and anterograde transport. Increased levels of retrograde motor protein subunits are associated with accumulation of membranous organelles distal to nodal complexes. Using cell transplantation, we show categorically that the axonal phenotype is related to the presence of the overlying Plp null myelin. Our data demonstrate a novel role for oligodendrocytes in the local regulation of axonal function and have implications for the axonal loss associated with secondary progressive multiple sclerosis

Can we project changes in fish abundance and distribution in response to climate?

Large scale and long-term changes in fish abundance and distribution in response to climate change have been simulated using both statistical and process-based models. However, national and regional fisheries management requires also shorter term projections on smaller spatial scales, and these need to be validated against fisheries data. A 26-year time series of fish surveys with high spatial resolution in the North East Atlantic provides a unique opportunity to assess the ability of models to correctly simulate the changes in fish distribution and abundance that occurred in response to climate variability and change. We use a dynamic bioclimate envelope model forced by physical-biogeochemical output from eight ocean models to simulate changes in fish abundance and distribution at scales down to a spatial resolution of 0.5°. When comparing with these simulations with annual fish survey data, we found the largest differences at the 0.5° scale. Differences between fishery model runs driven by different biogeochemical models decrease dramatically when results are aggregated to larger scales (e.g. the whole North Sea), to total catches rather than individual species or when the ensemble mean instead of individual simulations are used. Recent improvements in the fidelity of biogeochemical models translate into lower error rates in the fisheries simulations. However, predictions based on different biogeochemical models are often more similar to each other than they are to the survey data, except for some pelagic species. We conclude that model results can be used to guide fisheries management at larger spatial scales, but more caution is needed at smaller scales

EcoGEnIE 1.0: plankton ecology in the cGEnIE Earth system model

We present an extension to the carbon-centric Grid Enabled Integrated Earth system model (cGEnIE) that explicitly accounts for the growth and interaction of an arbitrary number of plankton species. The new package (ECOGEM) replaces the implicit, flux-based parameterisation of the plankton community currently employed, with explicitly resolved plankton populations and ecological dynamics. In ECOGEM, any number of plankton species, with ecophysiological traits (e.g. growth and grazing rates) assigned according to organism size and functional group (e.g. phytoplankton and zooplankton) can be incorporated at runtime. We illustrate the capability of the marine ecology enabled Earth system model (EcoGEnIE) by comparing results from one configuration of ECOGEM (with eight generic phytoplankton and zooplankton size classes) to climatological and seasonal observations. We find that the new ecological components of the model show reasonable agreement with both global-scale climatological and local-scale seasonal data. We also compare EcoGEnIE results to the existing biogeochemical incarnation of cGEnIE. We find that the resulting global-scale distributions of phosphate, iron, dissolved inorganic carbon, alkalinity, and oxygen are similar for both iterations of the model. A slight deterioration in some fields in EcoGEnIE (relative to the data) is observed, although we make no attempt to re-tune the overall marine cycling of carbon and nutrients here. The increased capabilities of EcoGEnIE in this regard will enable future exploration of the ecological community on much longer timescales than have previously been examined in global ocean ecosystem models and particularly for past climates and global biogeochemical cycles.</p

The grapevine uncharacterized intrinsic protein 1 (VvXIP1) is regulated by drought stress and transports glycerol, hydrogen peroxide, heavy metals but not water

A MIP (Major Intrinsic Protein) subfamily called Uncharacterized Intrinsic Proteins (XIP) was recently described in several fungi and eudicot plants. In this work, we cloned a XIP from grapevine, VvXIP1, and agrobacterium-mediated transformation studies in Nicotiana benthamiana revealed that the encoded aquaporin shows a preferential localization at the endoplasmic reticulum membrane. Stopped-flow spectrometry in vesicles from the aqy-null yeast strain YSH1172 overexpressing VvXIP1 showed that VvXIP1 is unable to transport water but is permeable to glycerol. Functional studies with the ROS sensitive probe CM-H(2)DCFDA in intact transformed yeasts showed that VvXIP1 is also able to permeate hydrogen peroxide (H2O2). Drop test growth assays showed that besides glycerol and H2O2, VvXIP1 also transports boric acid, copper, arsenic and nickel. Furthermore, we found that VvXIP1 transcripts were abundant in grapevine leaves from field grown plants and strongly repressed after the imposition of severe water-deficit conditions in potted vines. The observed downregulation of VvXIP1 expression in cultured grape cells in response to ABA and salt, together with the increased sensitivity to osmotic stress displayed by the aqy-null yeast overexpressing VvXIP1, corroborates the role of VvXIP1 in osmotic regulation besides its involvement in H2O2 transport and metal homeostasis.This work was supported by European Union Funds (FEDER/COMPETE Operational Competitiveness Programme) and Portuguese national Funds (FCT-Portuguese Foundation for Science and Technology): KBBE-2012-6-3117 "Inovinne", FCOMP-01-0124-FEDER-022692 and PTDC/AGR-ALI/100636/2008. HN (SFRH/BD/74257/2010) and APM (SFRH/BD/65046/2009) were supported by PhD grants from FCT. The Interuniversity Attraction Poles Programme-Belgian Science Policy (IAP7/29) and the Belgian French community ARC11/16-036 project.info:eu-repo/semantics/publishedVersio

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration

Resolving and parameterising the ocean mesoscale in earth system models

Purpose of Review. Assessment of the impact of ocean resolution in Earth System models on the mean state, variability, and future projections and discussion of prospects for improved parameterisations to represent the ocean mesoscale. Recent Findings. The majority of centres participating in CMIP6 employ ocean components with resolutions of about 1 degree in their full Earth Systemmodels (eddy-parameterising models). In contrast, there are alsomodels submitted toCMIP6 (both DECK and HighResMIP) that employ ocean components of approximately 1/4 degree and 1/10 degree (eddy-present and eddy-rich models). Evidence to date suggests that whether the ocean mesoscale is explicitly represented or parameterised affects not only the mean state of the ocean but also the climate variability and the future climate response, particularly in terms of the Atlantic meridional overturning circulation (AMOC) and the Southern Ocean. Recent developments in scale-aware parameterisations of the mesoscale are being developed and will be included in future Earth System models. Summary. Although the choice of ocean resolution in Earth System models will always be limited by computational considerations, for the foreseeable future, this choice is likely to affect projections of climate variability and change as well as other aspects of the Earth System. Future Earth System models will be able to choose increased ocean resolution and/or improved parameterisation of processes to capture physical processes with greater fidelity