Amyloid-beta/Fyn–Induced Synaptic, Network, and Cognitive Impairments Depend on Tau Levels in Multiple Mouse Models of Alzheimer’s Disease

Alzheimer\u27s disease (AD), the most common neurodegenerative disorder, is a growing public health problem and still lacks effective treatments. Recent evidence suggests that microtubule-associated protein tau may mediate amyloid-β peptide (Aβ) toxicity by modulating the tyrosine kinase Fyn.Weshowed previously that tau reduction prevents, and Fyn overexpression exacerbates, cognitive deficits in human amyloid precursor protein (hAPP) transgenic mice overexpressing Aβ. However, the mechanisms by which Aβ, tau, and Fyn cooperate in AD-related pathogenesis remain to be fully elucidated. Here we examined the synaptic and network effects of this pathogenic triad. Tau reduction prevented cognitive decline induced by synergistic effects of Aβ and Fyn. Tau reduction also prevented synaptic transmission and plasticity deficits in hAPP mice. Using electroencephalography to examine network effects, we found that tau reduction prevented spontaneous epileptiform activity in multiple lines of hAPP mice. Tau reduction also reduced the severity of spontaneous and chemically induced seizures in mice overexpressing both Aβ and Fyn. To better understand these protective effects, we recorded wholecell currents in acute hippocampal slices from hAPP mice with and without tau. hAPP mice with tau had increased spontaneous and evoked excitatory currents, reduced inhibitory currents, and NMDA receptor dysfunction. Tau reduction increased inhibitory currents and normalized excitation/inhibition balance and NMDA receptor-mediated currents in hAPP mice. Our results indicate that Aβ, tau, and Fyn jointly impair synaptic and network function and suggest that disrupting the copathogenic relationship between these factors could be of therapeutic benefit

Supporting Women Entrepreneurs in Ireland

Entrepreneurship development is an important requirement for achieving the goal of smart, sustainable and inclusive growth set out in the Europe 2020 strategy. It is also a means to respond to new economic challenges, to create jobs and to fight social and financial exclusion. The impact of the global financial and economic crisis calls for giving entrepreneurship and self-employment a stronger role in economic and social development policies. Inclusive entrepreneurship policies and programmes are particularly relevant for women who continue to face challenges in the labour market and are under-represented in entrepreneurship activities. However, the effectiveness of national, regional and local measures and actions to promote inclusive entrepreneurship development in Europe can be hindered by a fragmentation of responsibilities, resources and strategies, and a failure to understand the goals of inclusive entrepreneurship

The Wetland Intrinsic Potential tool: mapping wetland intrinsic potential through machine learning of multi-scale remote sensing proxies of wetland indicators

Accurate, unbiased wetland inventories are critical to monitor and protect wetlands from future harm or land conversion. However, most wetland inventories are constructed through manual image interpretation or automated classification of multi-band imagery and are biased towards wetlands that are easy to directly detect in aerial and satellite imagery. Wetlands that are obscured by forest canopy, that occur ephemerally, and that have no visible standing water are, therefore, often missing from wetland maps. To aid in the detection of these cryptic wetlands, we developed the Wetland Intrinsic Potential (WIP) tool, based on a wetland-indicator framework commonly used on the ground to detect wetlands through the presence of hydrophytic vegetation, hydrology, and hydric soils. Our tool uses a random forest model with spatially explicit input variables that represent all three wetland indicators, including novel multi-scale topographic indicators that represent the processes that drive wetland formation, to derive a map of wetland probability. With the ability to include multi-scale topographic indicators that help identify cryptic wetlands, the WIP tool can identify areas conducive to wetland formation while providing a flexible approach that can be adapted to diverse landscapes. For a study area in the Hoh River watershed in western Washington, USA, classification of the output probability with a threshold of 0.5 provided an overall accuracy of 91.97 %. Compared to the National Wetlands Inventory, the classified WIP tool output identified over 2 times the wetland area and reduced errors of omission from 47.5 % to 14.1 % but increased errors of commission from 1.9 % to 10.5 %. The WIP tool is implemented as an ArcGIS toolbox using a combination of R and Python scripts.</p

Advancements and opportunities to improve bottom–up estimates of global wetland methane emissions

Wetlands are the single largest natural source of atmospheric methane (CH4), contributing approximately 30% of total surface CH4 emissions, and they have been identified as the largest source of uncertainty in the global CH4 budget based on the most recent Global Carbon Project CH4 report. High uncertainties in the bottom-up estimates of wetland CH4 emissions pose significant challenges for accurately understanding their spatiotemporal variations, and for the scientific community to monitor wetland CH4 emissions from space. In fact, there are large disagreements between bottom-up estimates versus top-down estimates inferred from inversion of atmospheric CH4 concentrations. To address these critical gaps, we review recent development, validation, and applications of bottom-up estimates of global wetland CH4 emissions, as well as how they are used in top-down inversions. These bottom-up estimates, using (1) empirical biogeochemical modeling (e.g. WetCHARTs: 125-208 TgCH4 yr−1); (2) process-based biogeochemical modeling (e.g. WETCHIMP: 190 ± 39 TgCH4 yr−1); and (3) data-driven machine learning approach (e.g. UpCH4: 146 ± 43 TgCH4 yr−1). Bottom-up estimates are subject to significant uncertainties (∼80 Tg CH4 yr−1), and the ranges of different estimates do not overlap, further amplifying the overall uncertainty when combining multiple data products. These substantial uncertainties highlight gaps in our understanding of wetland CH4 biogeochemistry and wetland inundation dynamics. Major tropical and arctic wetland complexes are regional hotspots of CH4 emissions. However, the scarcity of satellite data over the tropics and northern high latitudes offer limited information for top-down inversions to improve bottom-up estimates. Recent advances in surface measurements of CH4 fluxes (e.g. FLUXNET-CH4) across a wide range of ecosystems including bogs, fens, marshes, and forest swamps provide an unprecedented opportunity to improve existing bottom-up estimates of wetland CH4 estimates. We suggest that continuous long-term surface measurements at representative wetlands, high fidelity wetland mapping, combined with an appropriate modeling framework, will be needed to significantly improve global estimates of wetland CH4 emissions. There is also a pressing unmet need for fine-resolution and high-precision satellite CH4 observations directed at wetlands

A review of carbon monitoring in wet carbon systems using remote sensing

Carbon monitoring is critical for the reporting and verification of carbon stocks and change. Remote sensing is a tool increasingly used to estimate the spatial heterogeneity, extent and change of carbon stocks within and across various systems. We designate the use of the term wet carbon system to the interconnected wetlands, ocean, river and streams, lakes and ponds, and permafrost, which are carbon-dense and vital conduits for carbon throughout the terrestrial and aquatic sections of the carbon cycle. We reviewed wet carbon monitoring studies that utilize earth observation to improve our knowledge of data gaps, methods, and future research recommendations. To achieve this, we conducted a systematic review collecting 1622 references and screening them with a combination of text matching and a panel of three experts. The search found 496 references, with an additional 78 references added by experts. Our study found considerable variability of the utilization of remote sensing and global wet carbon monitoring progress across the nine systems analyzed. The review highlighted that remote sensing is routinely used to globally map carbon in mangroves and oceans, whereas seagrass, terrestrial wetlands, tidal marshes, rivers, and permafrost would benefit from more accurate and comprehensive global maps of extent. We identified three critical gaps and twelve recommendations to continue progressing wet carbon systems and increase cross system scientific inquiry

Serotonin 3A Receptor Subtype as an Early and Protracted Marker of Cortical Interneuron Subpopulations

To identify neocortical neurons expressing the type 3 serotonergic receptor, here we used transgenic mice expressing the enhanced green fluorescent protein (GFP) under the control of the 5-HT3A promoter (5-HT3A:GFP mice). By means of whole-cell patch-clamp recordings, biocytin labeling, and single-cell reversed-transcriptase polymerase chain reaction on acute brain slices of 5-HT3A:GFP mice, we identified 2 populations of 5-HT3A-expressing interneurons within the somatosensory cortex. The first population was characterized by the frequent expression of the vasoactive intestinal peptide and a typical bipolar/bitufted morphology, whereas the second population expressed predominantly the neuropeptide Y and exhibited more complex dendritic arborizations. Most interneurons of this second group appeared very similar to neurogliaform cells according to their electrophysiological, molecular, and morphological properties. The combination of 5-bromo-2-deoxyuridine injections with 5-HT3A mRNA detection showed that cortical 5-HT3A interneurons are generated around embryonic day 14.5. Although at this stage the 5-HT3A receptor subunit is expressed in both the caudal ganglionic eminence and the entopeduncular area, homochronic in utero grafts experiments revealed that cortical 5-HT3A interneurons are mainly generated in the caudal ganglionic eminence. This protracted expression of the 5-HT3A subunit allowed us to study specific cortical interneuron populations from their birth to their final functional phenotype

Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb