Bioactive Secondary Metabolites from a New Terrestrial Streptomyces sp. TN262

During our search for Streptomyces spp. as new producers of bioactive secondary metabolites, the ethyl acetate extract of the new terrestrial Streptomyces isolate TN262 delivered eight antimicrobially active compounds. They were identified as 1-acetyl-β-carboline (1), tryptophol (2), cineromycin B (3), 2,3-dihydrocineromycin B (4), cyclo-(tyrosylprolyl) (5), 3-(hydroxyacetyl)-indole (6), brevianamide F (7), and cis-cyclo-(l-prolyl-l-leucyl) (8). Three further metabolites were detected in the unpolar fractions using GC–MS and tentatively assigned as benzophenone (9), N-butyl-benzenesulfonamide (10), and hexanedioic acid-bis-(2-ethylhexyl) ester (11). This last compound is known as plasticizer derivatives, but it has never been described from natural sources. In this article, we describe the identification of the new Streptomyces sp. isolate TN262 using its cultural characteristics, the nucleotide sequence of the corresponding 16S rRNA gene and the phylogenetic analysis, followed by optimization, large-scale fermentation, isolation of the bioactive constituents, and determination of their structures. The biological activity of compounds (2), (3), (4), and those of the unpolar fractions was addressed as well

Nematicidal activity of fervenulin isolated from a nematicidal actinomycete, Streptomyces sp. CMU-MH021, on Meloidogyne incognita

An isolate of the actinomycete, Streptomyces sp. CMU-MH021 produced secondary metabolites that inhibited egg hatch and increased juvenile mortality of the root-knot nematode Meloidogyne incognita in vitro. 16S rDNA gene sequencing showed that the isolate sequence was 99% identical to Streptomyces roseoverticillatus. The culture filtrates form different culture media were tested for nematocidal activity. The maximal activity against M. incognita was obtained by using modified basal (MB) medium. The nematicidal assay-directed fractionation of the culture broth delivered fervenulin (1) and isocoumarin (2). Fervenulin, a low molecular weight compound, shows a broad range of biological activities. However, nematicidal activity of fervenulin was not previously reported. The nematicidal activity of fervenulin (1) was assessed using the broth microdilution technique. The lowest minimum inhibitory concentrations (MICs) of the compound against egg hatch of M. incognita was 30 μg/ml and juvenile mortality of M. incognita increasing was observed at 120 μg/ml. Moreover, at the concentration of 250 μg/ml fervenulin (1) showed killing effect on second-stage nematode juveniles of M. incognita up to 100% after incubation for 96 h. Isocoumarin (2), another bioactive compound produced by Streptomyces sp. CMU-MH021, showed weak nematicidal activity with M. incognita

Atypical glandular cells in conventional cervical smears: Incidence and follow-up

BACKGROUND: Atypical glandular cells on cervical smears are often associated with clinically significant uterine lesions. The frequency and accuracy of AGC-NOS (i.e. atypical glandular cells, not otherwise specified) diagnoses, regardless of the gland cell type or the degree of suspicion, and their outcome were investigated. METHODS: From January 1, 1990 to December 31, 1999 a total of 261 patients had an AGC-NOS diagnosis made by conventional cervical Papanicolaou smear interpretation representing 0.05% of all Pap-smears analyzed at the national level. 191 (73.2%) patients had a subsequent histological examination, 8 samples were not representative by origin and were excluded. RESULTS: Out of 183 AGC-NOS diagnosed, 56.3% (103/183) were associated with tissue-proven precancerous and/or cancerous lesions, 44% being of endocervical and 56% of endometrial origin. 75% of all AGC-patients were asymptomatic. 66.7% (6/9) of the patients with subsequent invasive endocervical adenocarcinoma (AC) and 56% (28/50) of those patients with invasive endometrial AC were without clinical symptoms. 3 patients out of 9 with an invasive endocervical AC were 35 years of age or less. 10.1% and 12.3% of all 'new' tissue-proven invasive endocervical or endometrial AC respectively recorded by the national Morphologic Tumour Registry (MTR) were first identified by a cytological AGC-NOS diagnosis. CONCLUSION: Our findings emphasize the importance of the cytological AGC-category even in the absence of a precise origin or cell type specification. 56% of the AGC-diagnoses being associated with significant cancerous or precancerous conditions, a complete and careful evaluation is required

Multimodal Chemosensory Integration through the Maxillary Palp in Drosophila

Drosophila melanogaster has an olfactory organ called the maxillary palp. It is smaller and numerically simpler than the antenna, and its specific role in behavior has long been unclear. Because of its proximity to the mouthparts, I explored the possibility of a role in taste behavior. Maxillary palp was tuned to mediate odor-induced taste enhancement: a sucrose solution was more appealing when simultaneously presented with the odorant 4-methylphenol. The same result was observed with other odors that stimulate other types of olfactory receptor neuron in the maxillary palp. When an antennal olfactory receptor was genetically introduced in the maxillary palp, the fly interpreted a new odor as a sweet-enhancing smell. These results all point to taste enhancement as a function of the maxillary palp. It also opens the door for studying integration of multiple senses in a model organism

The Effects of Arbuscular Mycorrhizal Fungi on Direct and Indirect Defense Metabolites of Plantago lanceolata L.

Arbuscular mycorrhizal fungi can strongly influence the metabolism of their host plant, but their effect on plant defense mechanisms has not yet been thoroughly investigated. We studied how the principal direct defenses (iridoid glycosides) and indirect defenses (volatile organic compounds) of Plantago lanceolata L. are affected by insect herbivory and mechanical wounding. Volatile compounds were collected and quantified from mycorrhizal and non-mycorrhizal P. lanceolata plants that underwent three different treatments: 1) insect herbivory, 2) mechanical wounding, or 3) no damage. The iridoids aucubin and catalpol were extracted and quantified from the same plants. Emission of terpenoid volatiles was significantly higher after insect herbivory than after the other treatments. However, herbivore-damaged mycorrhizal plants emitted lower amounts of sesquiterpenes, but not monoterpenes, than herbivore-damaged non-mycorrhizal plants. In contrast, mycorrhizal infection increased the emission of the green leaf volatile (Z)-3-hexenyl acetate in untreated control plants, making it comparable to emission from mechanically wounded or herbivore-damaged plants whether or not they had mycorrhizal associates. Neither mycorrhization nor treatment had any influence on the levels of iridoid glycosides. Thus, mycorrhizal infection did not have any effect on the levels of direct defense compounds measured in P. lanceolata. However, the large decline in herbivore-induced sesquiterpene emission may have important implications for the indirect defense potential of this species

IL-33 Is Produced by Mast Cells and Regulates IgE-Dependent Inflammation

Background: IL-33 is a recently characterized IL-1 family cytokine and found to be expressed in inflammatory diseases, including severe asthma and inflammatory bowl disease. Recombinant IL-33 has been shown to enhance Th2-associated immune responses and potently increase mast cell proliferation and cytokine production. While IL-33 is constitutively expressed in endothelial and epithelial cells, where it may function as a transcriptional regulator, cellular sources of IL-33 and its role in inflammation remain unclear. Methodology/Principal Findings: Here, we identify mast cells as IL-33 producing cells. IgE/antigen activation of bone marrow-derived mast cells or a murine mast cell line (MC/9) significantly enhanced IL-33. Conversely, recombinant IL-33 directly activated mast cells to produce several cytokines including IL-4, IL-5 and IL-6 but not IL-33. We show that expression of IL-33 in response to IgE-activation required calcium and that ionomycin was sufficient to induce IL-33. In vivo, peritoneal mast cells expressed IL-33 and IL-33 levels were significantly lower within the skin of mast cell deficient mice, compared to littermate controls. Local activation of mast cells promotes edema, followed by the recruitment of inflammatory cells. We demonstrate using passive cutaneous anaphylaxis, a mast cell-dependent model, that deficiency in ST2 or antibody blockage of ST2 or IL-33 ablated the late phase inflammatory response but that the immediate phase response was unaffected. IL-33 levels in the skin were significantly elevated only during the late phase

Dental health in Dutch drug addicts

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