127 research outputs found

    Guiding the management of an agricultural pest: Indexing abundance of California meadow voles in artichoke fields

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    Nearly 100% of U.S. artichoke production comes from California and is concentrated in Monterey County. California meadow voles are damaging rodent pests that can threaten the profitability of growing artichokes. A practical population monitoring method can be invaluable to integrated pest management programs for guiding when and where control is needed and assessing control efficacy. The standard method for indexing vole populations in artichoke fields has been based on observing chewing on artichoke bracts placed throughout the field. Because toxicants are delivered on artichoke bracts, bias for population indexing is potentially introduced. We therefore compared artichoke bracts to nontoxic grain-based wax bait blocks as an alternative chewing medium for eliciting chewing observations for indexing abundance. We also compared the use of binary (presence-absence) observations of chewing to continuous measures (percent chewed). We considered the effect of three sizes of observation grids (4 x 4, 5 x 5, 6 x 6) for indexing.We conducted intensive trapping to determine number of voles known to be alive (KTBA) at each site as a basis for assessing which of the 12 indexing approaches (2 chewing mediums, 2 measurement types, 3 grid sizes) best tracked population abundance. The percent chewed on artichoke bracts for all grid sizes only marginally correlated with KTBA (~0.5), whereas percent chewed on bait blocks correlated very well with KTBA for all grid sizes (~0.9). Reducing continuous data to binary observations produced indices only weakly or negatively correlated with KTBA. Available resources would probably determine whether smaller grid sizes would be used for obtaining chewing observations

    Guiding the management of an agricultural pest: Indexing abundance of California meadow voles in artichoke fields

    Get PDF
    Nearly 100% of U.S. artichoke production comes from California and is concentrated in Monterey County. California meadow voles are damaging rodent pests that can threaten the profitability of growing artichokes. A practical population monitoring method can be invaluable to integrated pest management programs for guiding when and where control is needed and assessing control efficacy. The standard method for indexing vole populations in artichoke fields has been based on observing chewing on artichoke bracts placed throughout the field. Because toxicants are delivered on artichoke bracts, bias for population indexing is potentially introduced. We therefore compared artichoke bracts to nontoxic grain-based wax bait blocks as an alternative chewing medium for eliciting chewing observations for indexing abundance. We also compared the use of binary (presence-absence) observations of chewing to continuous measures (percent chewed). We considered the effect of three sizes of observation grids (4 x 4, 5 x 5, 6 x 6) for indexing.We conducted intensive trapping to determine number of voles known to be alive (KTBA) at each site as a basis for assessing which of the 12 indexing approaches (2 chewing mediums, 2 measurement types, 3 grid sizes) best tracked population abundance. The percent chewed on artichoke bracts for all grid sizes only marginally correlated with KTBA (~0.5), whereas percent chewed on bait blocks correlated very well with KTBA for all grid sizes (~0.9). Reducing continuous data to binary observations produced indices only weakly or negatively correlated with KTBA. Available resources would probably determine whether smaller grid sizes would be used for obtaining chewing observations

    Quality of life and persisting symptoms in intensive care unit survivors: implications for care after discharge

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    <p>Abstract</p> <p>Background</p> <p>We assessed the quality of life of ICU survivors using SF-36 at 4 months after ICU discharge and investigated any correlation of PCS and MCS with age, illness severity and hospital or ICU length of stay. We examined the relationship between these variables, persisting physical and psychological symptoms and the perceived benefit of individual patients of follow-up.</p> <p>Findings</p> <p>For one year, adult patients admitted for multiple organ or advanced respiratory support for greater than 48 hours to a 16-bedded teaching hospital general intensive care unit were identified. Those surviving to discharge were sent a questionnaire at 4 months following ICU discharge assessing quality of life and persisting symptoms. Demographic, length of stay and illness severity data were recorded. Higher or lower scores were divided at the median value. A two-tailed Students t-test assuming equal variances was used for normally-distributed data and Mann-Whitney tests for non-parametric data.</p> <p>87 of 175 questionnaires were returned (50%), but only 65 had sufficient data giving a final response rate of 37%. Elderly patients had increased MCS as compared with younger patients. The PCS was inversely related to hospital LOS. There was a significant correlation between the presence of psychological and physical symptoms and desire for follow-up.</p> <p>Conclusion</p> <p>Younger age and prolonged hospital stay are associated with lower mental or physical quality of life and may be targets for rehabilitation. Patients with persisting symptoms at 4 months view follow-up as beneficial and a simple screening questionnaire may identify those likely to attend outpatient services.</p

    IKK/NF-κB signaling contributes to glioblastoma stem cell maintenance

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    // Amanda L. Rinkenbaugh 1,2 , Patricia C. Cogswell 2,3 , Barbara Calamini 4 , Denise E. Dunn 4 , Anders I. Persson 5,6 , William A. Weiss 5,6 , Donald C. Lo 4 and Albert S. Baldwin 2 1 Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA 2 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA 3 Chordoma Foundation, Durham, NC, USA 4 Center for Drug Discovery and Department of Neurobiology, Duke University Medical Center, Durham, NC, USA 5 Helen Diller Family Comprehensive Cancer Center and Department of Neurology, University of California, San Francisco, CA, USA 6 Department of Neurological Surgery and Brain Tumor Research Center, University of California, San Francisco, CA, USA Correspondence to: Albert Baldwin, email: // Keywords : NF-κB, glioblastoma, cancer stem cells, tumor-initiating cells Received : March 14, 2016 Accepted : September 24, 2016 Published : October 06, 2016 Abstract Glioblastoma multiforme (GBM) carries a poor prognosis and continues to lack effective treatments. Glioblastoma stem cells (GSCs) drive tumor formation, invasion, and drug resistance and, as such, are the focus of studies to identify new therapies for disease control. Here, we identify the involvement of IKK and NF-κB signaling in the maintenance of GSCs. Inhibition of this pathway impairs self-renewal as analyzed in tumorsphere formation and GBM expansion as analyzed in brain slice culture. Interestingly, both the canonical and non-canonical branches of the NF-κB pathway are shown to contribute to this phenotype. One source of NF-κB activation in GBM involves the TGF-β/TAK1 signaling axis. Together, our results demonstrate a role for the NF-κB pathway in GSCs and provide a mechanistic basis for its potential as a therapeutic target in glioblastoma

    Flavour compounds in tomato fruits: identification of loci and potential pathways affecting volatile composition

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    The unique flavour of a tomato fruit is the sum of a complex interaction among sugars, acids, and a large set of volatile compounds. While it is generally acknowledged that the flavour of commercially produced tomatoes is inferior, the biochemical and genetic complexity of the trait has made breeding for improved flavour extremely difficult. The volatiles, in particular, present a major challenge for flavour improvement, being generated from a diverse set of lipid, amino acid, and carotenoid precursors. Very few genes controlling their biosynthesis have been identified. New quantitative trait loci (QTLs) that affect the volatile emissions of red-ripe fruits are described here. A population of introgression lines derived from a cross between the cultivated tomato Solanum lycopersicum and its wild relative, S. habrochaites, was characterized over multiple seasons and locations. A total of 30 QTLs affecting the emission of one or more volatiles were mapped. The data from this mapping project, combined with previously collected data on an IL population derived from a cross between S. lycopersicum and S. pennellii populations, were used to construct a correlational database. A metabolite tree derived from these data provides new insights into the pathways for the synthesis of several of these volatiles. One QTL is a novel locus affecting fruit carotenoid content on chromosome 2. Volatile emissions from this and other lines indicate that the linear and cyclic apocarotenoid volatiles are probably derived from separate carotenoid pools

    Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy.

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    Class B peptide hormone GPCRs are targets for the treatment of major chronic disease. Peptide ligands of these receptors display biased agonism and this may provide future therapeutic advantage. Recent active structures of the calcitonin (CT) and glucagon-like peptide-1 (GLP-1) receptors reveal distinct engagement of peptides with extracellular loops (ECLs) 2 and 3, and mutagenesis of the GLP-1R has implicated these loops in dynamics of receptor activation. In the current study, we have mutated ECLs 2 and 3 of the human CT receptor (CTR), to interrogate receptor expression, peptide affinity and efficacy. Integration of these data with insights from the CTR and GLP-1R active structures, revealed marked diversity in mechanisms of peptide engagement and receptor activation between the CTR and GLP-1R. While the CTR ECL2 played a key role in conformational propagation linked to Gs/cAMP signalling this was mechanistically distinct from that of GLP-1R ECL2. Moreover, ECL3 was a hotspot for distinct ligand- and pathway- specific effects, and this has implications for the future design of biased agonists of class B GPCRs

    Neutralization of Botulinum Neurotoxin by a Human Monoclonal Antibody Specific for the Catalytic Light Chain

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    Background: Botulinum neurotoxins (BoNT) are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC), a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored. Methods and Findings: We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A). The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro. Conclusions: An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components o

    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
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