529 research outputs found

    Use of In-Planta Solid Phase Sampling Devices to Delineate VOC Plumes

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    Plants Directly Interact with Surrounding Water, Air, and Soil, Collecting and Storing Chemicals and Elements from the Surrounding Environment. Two New and Innovative Sampling Methods in Which This Valuable Data Can Be Accessed to Replace as Well as Supplement Contaminated-Site Investigations Have Been Developed. When Determining the Extent of the Plume on a Contaminated Site, Groundwater Sampling May Be Limited Due to Time, Site Access, and Expense. by using New Techniques that Place Sampling Devices Inside the Trees on Site, We Can Sample Trees Naturally Occurring on a Contaminated Site or Those Planted in Phytoremediation or Redevelopment Efforts, Evaluate the Plume Size, and Even Monitor Changes in Concentration. These Methods Will Have a Minimal Footprint and Can Be Accomplished with Little Materials Cost, Time, or Labor Demands. These Quick Sampling Techniques Can Provide an Array of Data within a Short Amount of Time to Help the Efficiency in Placement of Groundwater Monitoring Wells, Saving Time and Money as Well as Undue Impact to the Ecosystems at Hand or Personal Property. © 2009 ASCE

    Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression

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    Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine’s antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology. This review aims to provide the reader with an understanding of neuroprogressive aspects of depressive pathology and how ketamine is suggested to act on it. Literature was identified through PubMed and Google Scholar, and the reference lists of retrieved articles. When reviewing the evidence of depressive pathology, a picture emerges of four elements interacting with each other to facilitate progressive worsening, namely stress, inflammation, neurotoxicity and neurodegeneration. Ketamine acts on all of these levels of pathology, with rapid and potent reductions of depressive symptoms. Converging evidence suggests that ketamine works to increase stress resilience and reverse stress-induced dysfunction, modulate systemic inflammation and neuroinflammation, attenuate neurotoxic processes and glial dysfunction, and facilitate synaptogenesis rather than neurodegeneration. Still, much remains to be revealed about ketamine’s antidepressant mechanisms of action, and research is lacking on the durability of effect. The findings discussed herein calls for more longitudinal approaches when determining efficacy and its relation to neuroprogressive factors, and could provide relevant considerations for clinical implementation.publishedVersio

    Time-Weighted Average SPME Analysis for in Planta Determination of CVOCs

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    The Potential of Phytoscreening for Plume Delineation at Contaminated Sites Has Promoted Interest in Innovative, Sensitive Contaminant Sampling Techniques. Solid-Phase Microextraction (SPME) Methods Have Been Developed, Offering Quick, Undemanding, Noninvasive Sampling Without the Use of Solvents. in This Study, Time-Weighted Average SPME (TWA-SPME) Sampling Was Evaluated for in Planta Quantification of Chlorinated Solvents. TWA-SPME Was Found to Have Increased Sensitivity over Headspace and Equilibrium SPME Sampling. using a Variety of Chlorinated Solvents and a Polydimethylsiloxane/carboxen (PDMS/CAR) SPME Fiber, Most Compounds Exhibited Near Linear or Linear Uptake over the Sampling Period. Smaller, Less Hydrophobic Compounds Exhibited More Nonlinearity Than Larger, More Hydrophobic Molecules. using a Specifically Designed in Planta Sampler, Field Sampling Was Conducted at a Site Contaminated with Chlorinated Solvents. Sampling with TWA-SPME Produced Instrument Responses Ranging from 5 to over 200 Times Higher Than Headspace Tree Core Sampling. This Work Demonstrates that TWA-SPME Can Be Used for in Planta Detection of a Broad Range of Chlorinated Solvents and Methods Can Likely Be Applied to Other Volatile and Semivolatile Organic Compounds. © 2012 American Chemical Society

    Duffy antigen receptor for chemokines and CXCL5 are essential for the recruitment of neutrophils in a multicellular model of rheumatoid arthritis synovium

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    OBJECTIVE: The role of chemokines and their transporters are poorly described in rheumatoid arthritis (RA). Evidence suggests that CXCL5 plays an important role as it is abundant in RA tissue and its neutralization moderates joint damage in animal models of arthritis. The chemokine transporter, Duffy Antigen Receptor for Chemokines (DARC), is also upregulated in early RA. Here we investigate the role of CXCL5 and DARC in regulating neutrophil recruitment using an in vitro model of the RA synovium. METHODS: To model the RA synovium, rheumatoid fibroblasts (RAF) were cocultured with endothelial cells (EC) for 24h. Gene expression in cocultured cells was investigated using TaqMan gene arrays. Roles of CXCL5 and DARC were determined by incorporating cocultures into a flow-based adhesion assay, where their function was demonstrated by blocking neutrophil recruitment with neutralizing reagents. RESULTS: EC-RAF coculture induced chemokine expression in both cell types. While CXC chemokines were modestly upregulated in EC, CXCL1, CXCL5 and CXCL8 expression were greatly increased in RAF. RAF also promoted the recruitment of flowing neutrophils to EC. Anti-CXCL5 antibody abolished neutrophil recruitment by neutralizing CXCL5 expressed on EC, or when used to immuno-deplete coculture conditioned medium. DARC was also induced on EC by coculture and an anti-Fy6 antibody or siRNA targeting of DARC expression effectively abolished neutrophil recruitment. CONCLUSION: For the first time in a model of human disease, the function of DARC has been demonstrated as essential for editing the chemokine signals presented by EC and for promoting unwanted leukocyte recruitment

    Pretreatment ethyl glucuronide levels predict response to a contingency management intervention for alcohol use disorders among adults with serious mental illness.

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    BACKGROUND AND OBJECTIVES: This study investigated if pretreatment ethyl glucuronide (EtG) levels corresponding to light (100 ng/mL), heavy (500 ng/mL), and very heavy (1,000 ng/mL) drinking predicted longest duration of alcohol abstinence (LDA) and proportion of EtG-negative urine tests in outpatients receiving a 12-week EtG-based contingency management (CM) intervention for alcohol dependence. METHODS: Participants were 40 adults diagnosed with alcohol use disorders and serious mental illness who submitted up to 12 urine samples for EtG analysis during a 4-week observation period and were then randomized to 12-weeks of CM for alcohol abstinence and addiction treatment attendance. Alcohol use outcomes during CM as assessed by EtG and self-report were compared across those who did and did not attain a pre-treatment average EtG level of 500 ng/mL-a level that equates to frequent heavy drinking. RESULTS: Only the 500 ng/mL cutoff was associated with significant differences in LDA and proportion of EtG-negative samples during CM. Those with a pre-treatment EtG \u3c 500 ng/mL attained a LDA 2.3 (alcohol) to 2.9 (drugs) weeks longer than pre-treatment heavy drinkers. DISCUSSION AND CONCLUSIONS: The EtG biomarker can be used to determine who will respond to a CM intervention for alcohol use disorders and could inform future trials that are designed to be tailored to individual patients. SCIENTIFIC SIGNIFICANCE: Results suggest pre-treatment EtG cutoffs equivalent to heavy and very heavy drinking predict outcomes in CM. (Am J Addict 2017;26:673-675)

    A Disorder-to-Order Transition Activates an ATP-Independent Membrane Protein Chaperone

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    The 43 kDa subunit of the chloroplast signal recognition particle, cpSRP43, is an ATP-independent chaperone essential for the biogenesis of the light harvesting chlorophyll-binding proteins (LHCP), the most abundant membrane protein family on earth. cpSRP43 is activated by a stromal factor, cpSRP54, to more effectively capture and solubilize LHCPs. The molecular mechanism underlying this chaperone activation is unclear. Here, a combination of hydrogen–deuterium exchange, electron paramagnetic resonance, and NMR spectroscopy experiments reveal that a disorder-to-order transition of the ankyrin repeat motifs in the substrate binding domain of cpSRP43 drives its activation. An analogous coil-to-helix transition in the bridging helix, which connects the ankyrin repeat motifs to the cpSRP54 binding site in the second chromodomain, mediates long-range allosteric communication of cpSRP43 with its activating binding partner. Our results provide a molecular model to explain how the conformational dynamics of cpSRP43 enables regulation of its chaperone activity and suggest a general mechanism by which ATP-independent chaperones with cooperatively folding domains can be regulated

    Structural and molecular rationale for the diversification of resistance mediated by the Antibiotic_NAT family

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    The environmental microbiome harbors a vast repertoire of antibiotic resistance genes (ARGs) which can serve as evolutionary predecessors for ARGs found in pathogenic bacteria, or can be directly mobilized to pathogens in the presence of selection pressures. Thus, ARGs from benign environmental bacteria are an important resource for understanding clinically relevant resistance. Here, we conduct a comprehensive functional analysis of the Antibiotic_NAT family of aminoglycoside acetyltransferases. We determined a pan-family antibiogram of 21 Antibiotic_NAT enzymes, including 8 derived from clinical isolates and 13 from environmental metagenomic samples. We find that environment-derived representatives confer high-level, broad-spectrum resistance, including against the atypical aminoglycoside apramycin, and that a metagenome-derived gene likely is ancestral to an aac(3) gene found in clinical isolates. Through crystallographic analysis, we rationalize the molecular basis for diversification of substrate specificity across the family. This work provides critical data on the molecular mechanism underpinning resistance to established and emergent aminoglycoside antibiotics and broadens our understanding of ARGs in the environment

    Biomarkers of post-discharge mortality among children with complicated severe acute malnutrition

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    High mortality after discharge from hospital following acute illness has been observed among children with Severe Acute Malnutrition (SAM). However, mechanisms that may be amenable to intervention to reduce risk are unknown. We performed a nested case-control study among HIV-uninfected children aged 2-59 months treated for complicated SAM according to WHO recommendations at four Kenyan hospitals. Blood was drawn from 1778 children when clinically judged stable before discharge from hospital. Cases were children who died within 60 days. Controls were randomly selected children who survived for one year without readmission to hospital. Untargeted proteomics, total protein, cytokines and chemokines, and leptin were assayed in plasma and corresponding biological processes determined. Among 121 cases and 120 controls, increased levels of calprotectin, von Willebrand factor, angiotensinogen, IL8, IL15, IP10, TNF alpha, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were associated with mortality after adjusting for possible confounders. Acute phase responses, cellular responses to lipopolysaccharide, neutrophil responses to bacteria, and endothelial responses were enriched among cases. Among apparently clinically stable children with SAM, a sepsis-like profile is associated with subsequent death. This may be due to ongoing bacterial infection, translocated bacterial products or deranged immune response during nutritional recovery
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