Improved analysis of propylene oxide, propylene chlorohydrin and propylene bromohydrin: Presentation

The benefits and deficiencies of several methods of analysis for PPO and PXH, including the aqueous extraction used in ASTA method 23.1 and the MTBE extraction method previously reported by the authors, will be discussed. Novel methods utilizing dynamic headspace extraction and solid phase microextraction (SPME) will also be reported with particular emphasis on preventing artefactual effects. Preliminary experiments have found that dynamic headspace sampling can lower detection limits by up to 3 orders of magnitude.The benefits and deficiencies of several methods of analysis for PPO and PXH, including the aqueous extraction used in ASTA method 23.1 and the MTBE extraction method previously reported by the authors, will be discussed. Novel methods utilizing dynamic headspace extraction and solid phase microextraction (SPME) will also be reported with particular emphasis on preventing artefactual effects. Preliminary experiments have found that dynamic headspace sampling can lower detection limits by up to 3 orders of magnitude

Sublethal exposure, insecticide resistance, and community stress

Insecticides are an invaluable pest management tool and anthropogenic stressors of widespread environmental occurrence that are subject to biased perceptions based on the targeted application, market value of use, and regulatory requirements. As a result, short-term and simplistic efforts focusing on lethal effects toward individual species and populations prevail. Holistic and comprehensive studies exploring rather common sublethal insecticide exposures are rare, particularly considering their potential role in structuring populations and communities in diverse environmental settings and potentially interfering in a range of ecological interactions. Studies on insecticide resistance, for example, do not go beyond population-based studies, disregarding temporal and spatial effects in the associated community, and rarely considering the whole of sublethal exposure. Some of these knowledge gaps are here recognized and explored

Sublethal exposure, insecticide resistance, and community stress

Insecticides are an invaluable pest management tool and anthropogenic stressors of widespread environmental occurrence that are subject to biased perceptions based on the targeted application, market value of use, and regulatory requirements. As a result, short-term and simplistic efforts focusing on lethal effects toward individual species and populations prevail. Holistic and comprehensive studies exploring rather common sublethal insecticide exposures are rare, particularly considering their potential role in structuring populations and communities in diverse environmental settings and potentially interfering in a range of ecological interactions. Studies on insecticide resistance, for example, do not go beyond population-based studies, disregarding temporal and spatial effects in the associated community, and rarely considering the whole of sublethal exposure. Some of these knowledge gaps are here recognized and explored

Identification of conformational epitopes for human IgG on Chemotaxis inhibitory protein of Staphylococcus aureus

<p>Abstract</p> <p>Background</p> <p>The Chemotaxis inhibitory protein of <it>Staphylococcus aureus </it>(CHIPS) blocks the Complement fragment C5a receptor (C5aR) and formylated peptide receptor (FPR) and is thereby a potent inhibitor of neutrophil chemotaxis and activation of inflammatory responses. The majority of the healthy human population has antibodies against CHIPS that have been shown to interfere with its function <it>in vitro</it>. The aim of this study was to define potential epitopes for human antibodies on the CHIPS surface. We also initiate the process to identify a mutated CHIPS molecule that is not efficiently recognized by preformed anti-CHIPS antibodies and retains anti-inflammatory activity.</p> <p>Results</p> <p>In this paper, we panned peptide displaying phage libraries against a pool of CHIPS specific affinity-purified polyclonal human IgG. The selected peptides could be divided into two groups of sequences. The first group was the most dominant with 36 of the 48 sequenced clones represented. Binding to human affinity-purified IgG was verified by ELISA for a selection of peptide sequences in phage format. For further analysis, one peptide was chemically synthesized and antibodies affinity-purified on this peptide were found to bind the CHIPS molecule as studied by ELISA and Surface Plasmon Resonance. Furthermore, seven potential conformational epitopes responsible for antibody recognition were identified by mapping phage selected peptide sequences on the CHIPS surface as defined in the NMR structure of the recombinant CHIPS_31–121protein. Mapped epitopes were verified by <it>in vitro </it>mutational analysis of the CHIPS molecule. Single mutations introduced in the proposed antibody epitopes were shown to decrease antibody binding to CHIPS. The biological function in terms of C5aR signaling was studied by flow cytometry. A few mutations were shown to affect this biological function as well as the antibody binding.</p> <p>Conclusion</p> <p>Conformational epitopes recognized by human antibodies have been mapped on the CHIPS surface and amino acid residues involved in both antibody and C5aR interaction could be defined. This information has implications for the development of an effective anti-inflammatory agent based on a functional CHIPS molecule with low interaction with human IgG.</p

Proteolysis of Human Thrombin Generates Novel Host Defense Peptides

The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of “classical” helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe

In-package nonthermal plasma degradation of pesticides on fresh produce

In-package nonthermal plasma (NTP) technology is a novel technology for the decontamination of foods and biological materials. This study presents the first report on the potential of the technology for the degradation of pesticide residues. A cocktail of pesticides, namely Azoxystrobin, Cyprodinil, Fludioxonil and Pyriproxyfen was tested on strawberries. The concentrations of these pesticides were monitored in priori and post- plasma treatment using GC-MS/MS. An applied voltage and time dependent degradation of the pesticides was observed for treatment voltages of 60, 70 and 80 kV and treatment durations ranging from 1 to 5 min, followed by 24 h in-pack storage. The electrical characterisation revealed the operation of the discharge in a stable filamentary regime. The discharge was found to generate reactive oxygen and excited nitrogen species as observed by optical emission spectroscopy