Heterogeneous reactions of particulate matter-bound PAHs and NPAHs with NO3/N2O5, OH radicals, and O3 under simulated long-range atmospheric transport conditions: reactivity and mutagenicity.

The heterogeneous reactions of ambient particulate matter (PM)-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) with NO3/N2O5, OH radicals, and O3 were studied in a laboratory photochemical chamber. Ambient PM2.5 and PM10 samples were collected from Beijing, China, and Riverside, California, and exposed under simulated atmospheric long-range transport conditions for O3 and OH and NO3 radicals. Changes in the masses of 23 PAHs and 20 NPAHs, as well as the direct and indirect-acting mutagenicity of the PM (determined using the Salmonella mutagenicity assay with TA98 strain), were measured prior to and after exposure to NO3/N2O5, OH radicals, and O3. In general, O3 exposure resulted in the highest relative degradation of PM-bound PAHs with more than four rings (benzo[a]pyrene was degraded equally well by O3 and NO3/N2O5). However, NPAHs were most effectively formed during the Beijing PM exposure to NO3/N2O5. In ambient air, 2-nitrofluoranthene (2-NF) is formed from the gas-phase NO3 radical- and OH radical-initiated reactions of fluoranthene, and 2-nitropyrene (2-NP) is formed from the gas-phase OH radical-initiated reaction of pyrene. There was no formation of 2-NF or 2-NP in any of the heterogeneous exposures, suggesting that gas-phase formation of NPAHs did not play an important role during chamber exposures. Exposure of Beijing PM to NO3/N2O5 resulted in an increase in direct-acting mutagenic activity which was associated with the formation of mutagenic NPAHs. No NPAH formation was observed in any of the exposures of the Riverside PM. This was likely due to the accumulation of atmospheric degradation products from gas-phase reactions of volatile species onto the surface of PM collected in Riverside prior to exposure in the chamber, thus decreasing the availability of PAHs for reaction

Revisiting benzene cluster cations for the chemical ionization of dimethyl sulfide and select volatile organic compounds

Benzene cluster cations were revisited as a sensitive and selective reagent ion for the chemical ionization of dimethyl sulfide (DMS) and a select group of volatile organic compounds (VOCs). Laboratory characterization was performed using both a new set of compounds (i.e., DMS, β-caryophyllene) as well as previously studied VOCs (i.e., isoprene, α-pinene). Using a field deployable chemical-ionization time-of-flight mass spectrometer (CI-ToFMS), benzene cluster cations demonstrated high sensitivity (> 1 ncps ppt^(−1)) to DMS, isoprene, and α-pinene standards. Parallel measurements conducted using a chemical-ionization quadrupole mass spectrometer, with a much weaker electric field, demonstrated that ion–molecule reactions likely proceed through a combination of ligand-switching and direct charge transfer mechanisms. Laboratory tests suggest that benzene cluster cations may be suitable for the selective ionization of sesquiterpenes, where minimal fragmentation ( 0.95, 10 s averages) over a wide range of sampling conditions

Advancing Genetic Selection and Behavioral Genomics of Working Dogs Through Collaborative Science

The ancient partnership between people and dogs is struggling to meet modern day needs, with demand exceeding our capacity to safely breed high-performing and healthy dogs. New statistical genetic approaches and genomic technology have the potential to revolutionize dog breeding, by transitioning from problematic phenotypic selection to methods that can preserve genetic diversity while increasing the proportion of successful dogs. To fully utilize this technology will require ultra large datasets, with hundreds of thousands of dogs. Today, dog breeders struggle to apply even the tools available now, stymied by the need for sophisticated data storage infrastructure and expertise in statistical genetics. Here, we review recent advances in animal breeding, and how a new approach to dog breeding would address the needs of working dog breeders today while also providing them with a path to realizing the next generation of technology. We provide a step-by-step guide for dog breeders to start implementing estimated breeding value selection in their programs now, and we describe how genotyping and DNA sequencing data, as it becomes more widely available, can be integrated into this approach. Finally, we call for data sharing among dog breeding programs as a path to achieving a future that can benefit all dogs, and their human partners too

Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice

<p>Abstract</p> <p>Background</p> <p>Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice.</p> <p>Results</p> <p>In order to test the hypothesis that arginase has a role in allergic airway inflammation we generated arginase I-deficient bone marrow (BM) chimeric mice. Following transfer of arginase I-deficient BM into irradiated recipient mice, arginase I expression was not required for hematopoietic reconstitution and baseline immunity. Arginase I deficiency in bone marrow-derived cells decreased allergen-induced lung arginase by 85.8 ± 5.6%. In contrast, arginase II-deficient mice had increased lung arginase activity following allergen challenge to a similar level to wild type mice. BM-derived arginase I was not required for allergen-elicited sensitization, recruitment of inflammatory cells in the lung, and proliferation of cells. Furthermore, allergen-induced airway hyperresponsiveness and collagen deposition were similar in arginase-deficient and wild type mice. Additionally, arginase II-deficient mice respond similarly to their control wild type mice with allergen-induced inflammation, airway hyperresponsiveness, proliferation and collagen deposition.</p> <p>Conclusion</p> <p>Bone marrow cell derived arginase I is the predominant source of allergen-induced lung arginase but is not required for allergen-induced inflammation, airway hyperresponsiveness or collagen deposition.</p

Revisiting benzene cluster cations for the chemical ionization of dimethyl sulfide and select volatile organic compounds

Benzene cluster cations were revisited as a sensitive and selective reagent ion for the chemical ionization of dimethyl sulfide (DMS) and a select group of volatile organic compounds (VOCs). Laboratory characterization was performed using both a new set of compounds (i.e., DMS, β-caryophyllene) as well as previously studied VOCs (i.e., isoprene, α-pinene). Using a field deployable chemical-ionization time-of-flight mass spectrometer (CI-ToFMS), benzene cluster cations demonstrated high sensitivity (> 1 ncps ppt^(−1)) to DMS, isoprene, and α-pinene standards. Parallel measurements conducted using a chemical-ionization quadrupole mass spectrometer, with a much weaker electric field, demonstrated that ion–molecule reactions likely proceed through a combination of ligand-switching and direct charge transfer mechanisms. Laboratory tests suggest that benzene cluster cations may be suitable for the selective ionization of sesquiterpenes, where minimal fragmentation ( 0.95, 10 s averages) over a wide range of sampling conditions

Heterogeneous Reactions of PM-Bound PAHs and NPAHs with NO₃/N₂O₅, OH Radicals, and O₃ under Simulated Long-Range Atmospheric Transport Conditions: Reactivity and Mutagenicity

The heterogeneous reactions of ambient particulate matter (PM)-bound polycyclic aromatic hydrocarbons (PAHs) and nitro-PAHs (NPAHs) with NO₃/N₂O₅, OH radicals, and O₃ were studied in a laboratory photochemical chamber. Ambient PM[subscript 2.5] and PM₁₀ samples were collected from Beijing, China and Riverside, California, and exposed under simulated atmospheric long-range transport conditions for O₃ and OH and NO₃ radicals. Changes in the masses of 23 PAHs and 20 NPAHs, as well as the direct and indirect-acting mutagenicity of the PM (determined using the Salmonella mutagenicity assay with TA98 strain), were measured prior to and after exposure to NO₃/N₂O₅, OH radicals, and O₃. In general, O₃ exposure resulted in the highest relative degradation of PM-bound PAHs with more than four rings (benzo[a]pyrene was degraded equally well by O₃ and NO₃/N₂O₅). However, NPAHs were most effectively formed during the Beijing PM exposure to NO₃/N₂O₅. In ambient air 2-nitrofluoranthene (2-NF) is formed from gas-phase NO₃ radical- and OH radical-initiated reactions of fluoranthene, and 2-nitropyrene (2-NP) is formed from gas-phase OH radical-initiated reaction of pyrene. There was no formation of 2-NF or 2-NP in any of the heterogeneous exposures, suggesting that gas-phase formation of NPAHs did not play an important role during chamber exposures. Exposure of Beijing PM to NO₃/N₂O₅ resulted in an increase in direct-acting mutagenic activity which was associated with the formation of mutagenic NPAHs. No NPAH formation was observed in any of the exposures of the Riverside PM. This was likely due to the accumulation of atmospheric degradation products from gas phase reactions of volatile species onto the surface of PM collected in Riverside prior to exposure in the chamber, thus decreasing the availability of PAHs for reaction

Novel Nitro-PAH Formation from Heterogeneous Reactions of PAHs with NO₂, NO₃/N₂O₅, and OH Radicals: Prediction, Laboratory Studies and Mutagenicity

The heterogeneous reactions of benzo[a]pyrene-d₁₂ (BaP-d₁₂), benzo[k]fluoranthene-d₁₂ (BkF-d₁₂), benzo[ghi]perylene-d₁₂ (BghiP-d₁₂), dibenzo[a,i]pyrene-d₁₄ (DaiP-d₁₄), and dibenzo[a,l]pyrene (DalP) with NO₂, NO₃/N₂O₅, and OH radicals were investigated at room temperature and atmospheric pressure in an indoor Teflon chamber and novel mono NO₂-DaiP, and mono NO₂-DalP products were identified. Quartz fiber filters (QFF) were used as a reaction surface and the filter extracts were analyzed by GC/MS for nitrated-PAHs (NPAHs) and tested in the Salmonella mutagenicity assay, using Salmonella typhimurium strain TA98 (with and without metabolic activation). In parallel to the laboratory experiments, a theoretical study was conducted to rationalize the formation of NPAH isomers based on the thermodynamic stability of OH-PAH intermediates, formed from OH-radical-initiated reactions. NO₂ and NO₃/N₂O₅ were effective oxidizing agents in transforming PAHs to NPAHs, with BaP-d₁₂ being the most readily nitrated. Reaction of BaP-d₁₂, BkF-d₁₂ and BghiP-d₁₂ with NO₂ and NO₃/N₂O₅ resulted in the formation of more than one mono-nitro isomer product, while the reaction of DaiP-d₁₄ and DalP resulted in the formation of only one mono-nitro isomer product. The direct-acting mutagenicity increased the most after NO₃/N₂O₅ exposure, particularly for BkF-d₁₂ in which di-NO₂-BkF-d₁₀ isomers were measured. The deuterium isotope effect study suggested that substitution of deuterium for hydrogen lowered both the direct and indirect acting mutagenicity of NPAHs and may result in an underestimation of the mutagenicity of the novel NPAHs identified in this study.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the American Chemical Society and can be found at: http://pubs.acs.org/journal/esthag

NLRX1 Protein Attenuates Inflammatory Responses to Infection by Interfering with the RIG-I-MAVS and TRAF6-NF-κB Signaling Pathways

The nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins regulate innate immunity. Although the positive regulatory impact of NLRs is clear, their inhibitory roles are not well defined. We showed Nlrx1−/− mice exhibited increased expression of antiviral signaling molecules IFN-β, STAT2, OAS1 and IL-6 after influenza virus infection. Consistent with increased inflammation, Nlrx1−/− mice exhibited marked morbidity and histopathology. Infection of these mice with an influenza strain that carries a mutated NS-1 protein, which normally prevents IFN induction by interaction with RNA and the intracellular RNA sensor RIG-I, further exacerbated IL-6 and type I IFN signaling. NLRX1 also weakened cytokine responses to the 2009 H1N1 pandemic influenza virus in human cells. Mechanistically, Nlrx1 deletion led to constitutive interaction of MAVS and RIG-I. Additionally, an inhibitory function is identified for NLRX1 during LPS-activation of macrophages where the MAVS-RIG-I pathway was not involved. NLRX1 interacts with TRAF6 and inhibits NF-κB activation. Thus, NLRX1 functions as a checkpoint of overzealous inflammation

Cannabinoid Agonists Inhibit Neuropathic Pain Induced by Brachial Plexus Avulsion in Mice by Affecting Glial Cells and MAP Kinases

Many studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.Mice underwent BPA or sham surgery. The mRNA levels and protein expression of CB(1) and CB(2) receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5(th) and 30(th) days after surgery. We observed a marked increase in CB(1) and CB(2) receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5(th) or 30(th) day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30(th) day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5(th) and 30(th) days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5(th) and 30(th) days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30(th) day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.Our results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states

Guidelines and Recommendations on Yeast Cell Death Nomenclature

Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research