Comparative assessment of the effects of DREADDs and endogenously expressed GPCRs in hippocampal astrocytes on synaptic activity and memory

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) have proven themselves as one of the key in vivo techniques of modern neuroscience, allowing for unprecedented access to cellular manipulations in living animals. With respect to astrocyte research, DREADDs have become a popular method to examine the functional aspects of astrocyte activity, particularly G-protein coupled receptor (GPCR)-mediated intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) dynamics. With this method it has become possible to directly link the physiological aspects of astrocytic function to cognitive processes such as memory. As a result, a multitude of studies have explored the impact of DREADD activation in astrocytes on synaptic activity and memory. However, the emergence of varying results prompts us to reconsider the degree to which DREADDs expressed in astrocytes accurately mimic endogenous GPCR activity. Here we compare the major downstream signaling mechanisms, synaptic, and behavioral effects of stimulating Gq-, Gs-, and Gi-DREADDs in hippocampal astrocytes of adult mice to those of endogenously expressed GPCRs

Environmental Assessment of Soil for Monitoring Volume I: Indicators & Criteria

The ENVASSO Project (Contract 022713) was funded 2006-8, under the European Commission 6th Framework Programme of Research, with the objective of defining and documenting a soil monitoring system appropriate for soil protection at continental level. The ENVASSO Consortium, comprising 37 partners drawn from 25 EU Member States, reviewed soil indicators, identified existing soil inventories and monitoring programmes in the Member States, designed and programmed a database management system to capture, store and supply soil profile data, and drafted procedures and protocols appropriate for inclusion in a European soil monitoring network of sites that are geo-referenced and at which a qualified sampling process is or could be conducted. Volume I, one of six describing the results of the ENVASSO Project, identifies 290 potential indicators relating to 188 key issues for the following nine threats to soil: erosion, organic matter decline, contamination, sealing, compaction, loss of biodiversity, salinisation, landslides and desertification. Sixty candidate indicators that address 27 key issues, covering all these threats, were selected on the basis of their thematic relevance, policy relevance and data availability. Baseline and threshold values are presented and detailed Fact Sheets describe three priority indicators for each soil threat.JRC.DDG.H.7-Land management and natural hazard

Colony-Stimulating Factor 1 Receptor (CSF1R) Regulates Microglia Density and Distribution, but Not Microglia Differentiation In Vivo

Microglia are brain-resident macrophages with trophic and phagocytic functions. Dominant loss-of-function mutations in a key microglia regulator, colony-stimulating factor 1 receptor (CSF1R), cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a progressive white matter disorder. Because it remains unclear precisely how CSF1R mutations affect microglia, we generated an allelic series of csf1r mutants in zebrafish to identify csf1r-dependent microglia changes. We found that csf1r mutations led to aberrant microglia density and distribution and regional loss of microglia. The remaining microglia still had a microglia-specific gene expression signature, indicating that they had differentiated normally. Strikingly, we also observed lower microglia numbers and widespread microglia depletion in postmortem brain tissue of ALSP patients. Both in zebrafish and in human disease, local microglia loss also presented in regions without obvious pathology. Together, this implies that CSF1R mainly regulates microglia density and that early loss of microglia may contribute to ALSP pathogenesis. Oosterhof et al. show that colony-stimulating factor 1 receptor (CSF1R) primarily regulates microglia density and not their normal differentiation. In addition, they find widespread depletion of microglia in CSF1R-haploinsufficient zebrafish and leukodystrophy patients, also in the absence of pathology, indicating that microglia depletion may contribute to loss of white matter

COLD GASS, an IRAM Legacy Survey of Molecular Gas in Massive Galaxies: II. The non-universality of the Molecular Gas Depletion Timescale

We study the relation between molecular gas and star formation in a volume-limited sample of 222 galaxies from the COLD GASS survey, with measurements of the CO(1-0) line from the IRAM 30m telescope. The galaxies are at redshifts 0.025<z<0.05 and have stellar masses in the range 10.0<log(M*/Msun)<11.5. The IRAM measurements are complemented by deep Arecibo HI observations and homogeneous SDSS and GALEX photometry. A reference sample that includes both UV and far-IR data is used to calibrate our estimates of star formation rates from the seven optical/UV bands. The mean molecular gas depletion timescale, tdep(H2), for all the galaxies in our sample is 1 Gyr, however tdep(H2) increases by a factor of 6 from a value of ~0.5 Gyr for galaxies with stellar masses of 10^10 Msun to ~3 Gyr for galaxies with masses of a few times 10^11 Msun. In contrast, the atomic gas depletion timescale remains contant at a value of around 3 Gyr. This implies that in high mass galaxies, molecular and atomic gas depletion timescales are comparable, but in low mass galaxies, molecular gas is being consumed much more quickly than atomic gas. The strongest dependences of tdep(H2) are on the stellar mass of the galaxy (parameterized as log tdep(H2)= (0.36+/-0.07)(log M* - 10.70)+(9.03+/-0.99)), and on the specific star formation rate. A single tdep(H2) versus sSFR relation is able to fit both "normal" star-forming galaxies in our COLD GASS sample, as well as more extreme starburst galaxies (LIRGs and ULIRGs), which have tdep(H2) < 10^8 yr. Normal galaxies at z=1-2 are displaced with respect to the local galaxy population in the tdep(H2) versus sSFR plane and have molecular gas depletion times that are a factor of 3-5 times longer at a given value of sSFR due to their significantly larger gas fractions.Comment: Accepted for publication in MNRAS. 19 pages, 11 figure

Selective-area chemical beam epitaxy of in-plane InAs one-dimensional channels grown on InP(001), InP(111)B, and InP(110) surfaces

We report on the selective-area chemical beam epitaxial growth of InAs in-plane, one-dimensional (1-D) channels using patterned SiO$_{2}$-coated InP(001), InP(111)B, and InP(110) substrates to establish a scalable platform for topological superconductor networks. Top-view scanning electron micrographs show excellent surface selectivity and dependence of major facet planes on the substrate orientations and ridge directions, and the ratios of the surface energies of the major facet planes were estimated. Detailed structural properties and defects in the InAs nanowires (NWs) were characterized by transmission electron microscopic analysis of cross-sections perpendicular to the NW ridge direction and along the NW ridge direction. Electrical transport properties of the InAs NWs were investigated using Hall bars, a field effect mobility device, a quantum dot, and an Aharonov-Bohm loop device, which reflect the strong spin-orbit interaction and phase-coherent transport characteristic in the selectively grown InAs systems. This study demonstrates that selective-area chemical beam epitaxy is a scalable approach to realize semiconductor 1-D channel networks with the excellent surface selectivity and this material system is suitable for quantum transport studies

The impact of alternative trait-scaling hypotheses for the maximum photosynthetic carboxylation rate (Vcmax) on global gross primary production

The maximum photosynthetic carboxylation rate (Vcmax) is an influential plant trait that has multiple scaling hypotheses, which is a source of uncertainty in predictive understanding of global gross primary production (GPP). Four trait-scaling hypotheses (plant functional type, nutrient limitation, environmental filtering, and plant plasticity) with nine specific implementations were used to predict global Vcmax distributions and their impact on global GPP in the Sheffield Dynamic Global Vegetation Model (SDGVM). Global GPP varied from 108.1 to 128.2 PgC yr−1, 65% of the range of a recent model intercomparison of global GPP. The variation in GPP propagated through to a 27% coefficient of variation in net biome productivity (NBP). All hypotheses produced global GPP that was highly correlated (r = 0.85–0.91) with three proxies of global GPP. Plant functional type-based nutrient limitation, underpinned by a core SDGVM hypothesis that plant nitrogen (N) status is inversely related to increasing costs of N acquisition with increasing soil carbon, adequately reproduced global GPP distributions. Further improvement could be achieved with accurate representation of water sensitivity and agriculture in SDGVM. Mismatch between environmental filtering (the most data-driven hypothesis) and GPP suggested that greater effort is needed understand Vcmax variation in the field, particularly in northern latitudes

The Assembly History of Disk Galaxies: I - The Tully-Fisher Relation to z~1.3 from Deep Exposures with DEIMOS

We present new measures of the evolving scaling relations between stellar mass, luminosity and rotational velocity for a morphologically-inclusive sample of 129 disk-like galaxies with z_AB<22.5 in the redshift range 0.2<z<1.3, based on spectra from DEIMOS on the Keck II telescope, multi-color HST ACS photometry, and ground-based Ks-band imaging. A unique feature of our survey is the extended spectroscopic integration times, leading to significant improvements in determining characteristic rotational velocities for each galaxy. Rotation curves are reliably traced to the radius where they begin to flatten for ~90% of our sample, and we model the HST-resolved bulge and disk components in order to accurately de-project our measured velocities, accounting for seeing and dispersion. We demonstrate the merit of these advances by recovering an intrinsic scatter on the stellar mass Tully-Fisher relation a factor of 2-3 less than in previous studies at intermediate redshift and comparable to that of locally-determined relations. With our increased precision, we find the relation is well-established by ~1, with no significant evolution to ~0.3, \DeltaM_stellar ~ 0.04+/-0.07 dex. A clearer trend of evolution is seen in the B-band Tully-Fisher relation corresponding to a decline in luminosity of \DeltaM_B ~ 0.85+/-0.28 magnitudes at fixed velocity over the same redshift range, reflecting the changes in star formation over this period. As an illustration of the opportunities possible when gas masses are available for a sample such as ours, we show how our dynamical and stellar mass data can be used to evaluate the likely contributions of baryons and dark matter to the assembly history of spiral galaxies.Comment: 22 pages, 11 figures, Accepted for publication in the Astrophysical Journa

Biochars in soils : towards the required level of scientific understanding

Key priorities in biochar research for future guidance of sustainable policy development have been identified by expert assessment within the COST Action TD1107. The current level of scientific understanding (LOSU) regarding the consequences of biochar application to soil were explored. Five broad thematic areas of biochar research were addressed: soil biodiversity and ecotoxicology, soil organic matter and greenhouse gas (GHG) emissions, soil physical properties, nutrient cycles and crop production, and soil remediation. The highest future research priorities regarding biochar's effects in soils were: functional redundancy within soil microbial communities, bioavailability of biochar's contaminants to soil biota, soil organic matter stability, GHG emissions, soil formation, soil hydrology, nutrient cycling due to microbial priming as well as altered rhizosphere ecology, and soil pH buffering capacity. Methodological and other constraints to achieve the required LOSU are discussed and options for efficient progress of biochar research and sustainable application to soil are presented.Peer reviewe

Early amyloid-induced changes in microglia gene expression in male APP/PS1 mice

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia, characterized by deposition of extracellular amyloid-beta (Aβ) aggregates and intraneuronal hyperphosphorylated Tau. Many AD risk genes, identified in genome-wide association studies (GWAS), are expressed in microglia, the innate immune cells of the central nervous system. Specific subtypes of microglia emerged in relation to AD pathology, such as disease-associated microglia (DAMs), which increased in number with age in amyloid mouse models and in human AD cases. However, the initial transcriptional changes in these microglia in response to amyloid are still unknown. Here, to determine early changes in microglia gene expression, hippocampal microglia from male APPswe/PS1dE9 (APP/PS1) mice and wild-type littermates were isolated and analyzed by RNA sequencing (RNA-seq). By bulk RNA-seq, transcriptomic changes were detected in hippocampal microglia from 6-months-old APP/PS1 mice. By performing single-cell RNA-seq of CD11c-positive and negative microglia from 6-months-old APP/PS1 mice and analysis of the transcriptional trajectory from homeostatic to CD11c-positive microglia, we identified a set of genes that potentially reflect the initial response of microglia to Aβ