GCH1 deficiency activates brain innate immune response and impairs tyrosine hydroxylase homeostasis

The Parkinson’s disease (PD) risk gene GTP cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in tetrahydrobiopterin (BH4) synthesis, an essential cofactor in the synthesis of monoaminergic neurotransmitters. To investigate the mechanisms by which GCH1 deficiency may contribute to PD, we generated a loss of function zebrafish gch1 mutant (gch1-/-), using CRISPR/Cas technology. gch1-/- zebrafish develop marked monoaminergic neurotransmitter deficiencies by 5 dpf, movement deficits by 8 dpf and lethality by 12 dpf. Tyrosine hydroxylase protein levels were markedly reduced without loss of ascending dopaminergic (DAergic) neurons. L-Dopa treatment of gch1-/- larvae improved survival without ameliorating the motor phenotype. RNAseq of gch1-/- larval brain tissue identified highly upregulated transcripts involved in innate immune response. Subsequent experiments provided morphological and functional evidence of microglial activation in gch1-/-. The results of our study suggest that GCH1 deficiency may unmask early, subclinical parkinsonism and only indirectly contribute to neuronal cell death via immune-mediated mechanisms. Our work highlights the importance of functional validation for GWAS risk factors and further emphasises the important role of inflammation in the pathogenesis of PD

Turfgrass research report 1995

Postemergence herbicide efficacy on crabgrass / John R. Street and Renee M. Stewart -- Preemergence herbicide efficacy on crabgrass / John R. Street and Renee M. Stewart --Preemergent common chickweed weed control evaluation / William Pound -- Preemergent purple dead nettle weed control evaluation / William Pound -- General turfgrass broadleaf weed control evaluation / William Pound -- Finale/Roundup herbicide demonstration evaluation / William Pound -- Ground ivy control evaluation / William Pound -- Manage yellow nutsedge control evaluation / William Pound -- Alternative Turflon solvent tolerance evaluation / William Pound -- Wild violet control evaluation / William Pound --Leaf spot study, 1995 / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Leaf spot control study - Galena, Ohio / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Red thread control study, 1995 / Joe Rimelspach, Karl Danneberger -- Brown patch study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Brown patch (Rhizoctonia solani) curative study / Joe Rimelspach, Karl Danneberger and Jill Taylor -- Preventive dollar spot (Sclerotinia homoeocarpa) control study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Take-All control study / Joe Rimelspach and Karl Danneberger -- Yellow tuft study, 1995 / Joe Rimelspach, Karl Danneberger, Joseph Vagnier and Jill Taylor -- Summer patch control study / Rob Golembiewski, Joe Rimelspach and Karl Danneberger -- Sentinel and Daconil Ultrex gallonage study: influence on dollar spot control / Karl Danneberger and Jill Taylor -- Pink snow mold control study, 1994-1995 / Jill Taylor, Joe Rimelspach and Karl Danneberger -- Control of black cutworm, Agrotis ipsilon (Hufnagel), and sod webworms (Pyralidae: Crambinae) on short cut bentgrass, Agrostis palustris Hudson-1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Control of black cutworm, Agrotis ipsilon (Hufnagel), and sod webworms (Pyralidae: Crambinae) on short cut bentgrass, Agrostis palustris Hudson using spinosad formulations -1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Applications of insecticides for control of second generation hairy chinch bugs in turfgrass -1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Preventive application of insecticides for control of black turfgrass Ataenius larvae on golf course fairways, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Spring application of chemical and biological insecticides for control of overwintered white grubs in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Influence of post-treatment irrigation on the efficacy of RH 0345 and Merit applied at the time of egg hatch for control of Japanese beetle larvae in turf, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Application of various insecticides for preventive control of Japanese Beetle larvae in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Chemical and biological insecticides applied for control of white grubs in turfgrass, 1995 / David J. Shetlar, Harry D. Niemczyk and Kevin T. Power -- Nitrogen source, rate, and timing effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- Natural organic source evaluation on a Kentucky bluegrass-perennial ryegrass mixture / John R. Street and Renee M. Stewart -- Nitrogen source, rate, and timing effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- Polymer-coated nitrogen source effect on Kentucky bluegrass / John R. Street and Renee M. Stewart -- 1993 NTEP bentgrass test (fairway/tee) / Jill A. Taylor -- 1993 NTEP fineleaf fescue test / Jill Taylor -- 1994 NTEP perennial ryegrass test / Jill Taylor -- 'Primo' growth regulator evaluation on creeping bentgrass / William Pound -- Bermudagrass management study / John Street and Jill Taylor -- Electrophoretic evaluation of esterase isozymes from turfgrass seed blends and mixtures / G. E. Bell, M. B. McDonald Jr. and T. K. Danneberger -- Computer Imaging of Electrophoretic Gels / G. E. Bell, M. B. McDonald Jr., T. K. Danneberger and S. K. St. Martin -- Evaluation of Kentucky bluegrass blends using isoelectric focusing and computer imaging / G. E. Bell, M. B. McDonald Jr. and T. K. Danneberger -- Identification of RAFLP markers in perennial ryegrass / Patricia M. Sweeney and Karl Danneberger -- RAPD analysis of dry turfgrass seed / Patricia Sweeney, Robert Golembiewski and Karl Danneberge

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Simplistic Attachment and Multispectral Imaging with Semiconductor Nanocrystals

Advances in spectral deconvolution technologies are rapidly enabling researchers to replace or enhance traditional epifluorescence microscopes with instruments capable of detecting numerous markers simultaneously in a multiplexed fashion. While significantly expediting sample throughput and elucidating sample information, this technology is limited by the spectral width of common fluorescence reporters. Semiconductor nanocrystals (NC’s) are very bright, narrow band fluorescence emitters with great potential for multiplexed fluorescence detection, however the availability of NC’s with facile attachment chemistries to targeting molecules has been a severe limitation to the advancement of NC technology in applications such as immunocytochemistry and immunohistochemistry. Here we report the development of simple, yet novel attachment chemistries for antibodies onto NC’s and demonstrate how spectral deconvolution technology enables the multiplexed detection of 5 distinct NC-antibody conjugates with fluorescence emission wavelengths separated by as little as 20 nm

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Self-affirmation improves performance on tasks related to executive functioning

Objectives: The current study explored the effect of self-affirmation on two aspects of performance that have been related to executive functioning: working memory (assessed by a 2-back task) and inhibition (assessed by a Stroop task). The goal was to establish whether self-affirmation improved performance on these tasks. Method: Participants (N = 83) were randomized to either a self-affirmation or a control task and then completed the computerized tasks, in a fixed sequence. Results: Self-affirmed participants performed better than non-affirmed participants on both tasks. Conclusion: Self-affirmation can improve aspects of performance related to executive functioning. This finding may help to explain the wide range of beneficial effects that self-affirmation can have on cognition and behavior

Mapping hydroxyl variability throughout the global remote troposphere via synthesis of airborne and satellite formaldehyde observations

The hydroxyl radical (OH) fuels tropospheric ozone production and governs the lifetime of methane and many other gases. Existing methods to quantify global OH are limited to annual and global-to-hemispheric averages. Finer resolution is essential for isolating model deficiencies and building process-level understanding. In situ observations from the Atmospheric Tomography (ATom) mission demonstrate that remote tropospheric OH is tightly coupled to the production and loss of formaldehyde (HCHO), a major hydrocarbon oxidation product. Synthesis of this relationship with satellite-based HCHO retrievals and model-derived HCHO loss frequencies yields a map of total-column OH abundance throughout the remote troposphere (up to 70% of tropospheric mass) over the first two ATom missions (August 2016 and February 2017). This dataset offers unique insights on near-global oxidizing capacity. OH exhibits significant seasonality within individual hemispheres, but the domain mean concentration is nearly identical for both seasons (1.03 ± 0.25 × 10^6 cm^(−3)), and the biseasonal average North/South Hemisphere ratio is 0.89 ± 0.06, consistent with a balance of OH sources and sinks across the remote troposphere. Regional phenomena are also highlighted, such as a 10-fold OH depression in the Tropical West Pacific and enhancements in the East Pacific and South Atlantic. This method is complementary to budget-based global OH constraints and can help elucidate the spatial and temporal variability of OH production and methane loss

Experimental and modelling study of fatigue crack initiation in an aluminium beam with a hole under 4-point bending

Slip band formation and crack initiation during cyclic fatigue were investigated by in-situ experiments and non-local CPFEM simulations systematically. Experimental techniques including EBSD, digital image correlation (DIC) and SEM have been used to obtain consistent grain orientations, local strains, as well as the locations where slip bands and micro-cracks form on the sample surface. The realistic microstructure based on the EBSD map has been generated and used for finite element modelling. An advanced non-local crystal plasticity model, which considers the isotropic and kinematic hardening of the plastic strain gradient, has been adopted. The simulation results match well the corresponding experimental results. It was found that total strain and averaged slip on all slip systems, combined with accumulated slip on specific slip planes help predict the location and orientation of slip bands and micro-crack initiation correctly. Furthermore, a fatigue indicating parameter based on competition between maximum slip and the total slip has been proposed to reproduce the experimental observations