306 research outputs found
Drazepinone, a trisubstituted tetrahydronaphthofuroazepinone with herbicidal activity produced by Drechslera siccans
When grown in a minimal-defined medium, a strain of Drechslera siccans, a pathogenic fungus isolated from seeds of Lolium perenne, produced phytotoxic metabolites. This strain is one of the best toxin producers among several grass pathogenic fungal strains collected and tested to find phytotoxins to be used as natural herbicides of monocot weeds. From the culture filtrates of D. siccans, we isolated a new phytotoxic trisubstituted naphthofuroazepinone, named drazepinone, and characterised it as a 3,5,12a-trimethyl-2,5,5a,12a-tetrahydro- 1H-naphtho[2′,3′:4,5]furo[2,3-b]azepin-2-one. Assayed at 2 μg μl-1 solution the novel metabolite proved to have broad-spectrum herbicidal properties, without antibacterial and antifungal activities, and low zootoxic activity. Its original chemical structure and the interesting biological properties make drazepinone a potential natural herbicide. © 2005 Elsevier Ltd. All rights reserved
Antiviral Property of the Fungal Metabolite 3-O-Methylfunicone in Bovine Herpesvirus 1 Infection
Bovine herpesvirus type-1 (BoHV-1) is a widespread pathogen that provokes infectious rhinotracheitis and polymicrobial infections in cattle, resulting in serious economic losses to the farm animal industry and trade restrictions. To date, non-toxic active drugs against BoHV-1 are not available. The exploitation of bioactive properties of microbial products is of great pharmaceutical interest. In fact, fungi are a promising source of novel drugs with a broad spectrum of activities and functions, including antiviral properties. Hence, the potential antiviral properties of 3-O-methylfunicone (OMF), a secondary metabolite produced by Talaromyces pinophilus, were evaluated on BoHV-1. In this study, during BoHV-1 infection in bovine cells (MDBK), the non-toxic concentration of 5 µM OMF considerably reduced signs of cell death and increased cell proliferation. Furthermore, OMF significantly decreased the virus titer as well as the cytopathic effect and strongly inhibited the expression of bICP0, the major regulatory protein in the BoHV-1 lytic cycle. These findings were accompanied by a considerable up-regulation in the expression of the aryl hydrocarbon receptor (AhR), a multifunctional transcription factor also linked to the host’s response to a herpesvirus infection. Overall, our results suggest that by involving AhR, OMF shows potential against a BoHV-1 infection
In Vitro Evaluation of Antiviral Activities of Funicone-like Compounds Vermistatin and Penisimplicissin against Canine Coronavirus Infection
Recent studies have demonstrated that 3-O-methylfunicone (OMF), a fungal secondary metabolite from Talaromyces pinophilus belonging to the class of funicone-like compounds, has antiviral activity against canine coronaviruses (CCoV), which causes enteritis in dogs. Herein, we selected two additional funicone-like compounds named vermistatin (VER) and penisimplicissin (PS) and investigated their inhibitory activity towards CCoV infection. Thus, both compounds have been tested for their cytotoxicity and for antiviral activity against CCoV in A72 cells, a fibrosarcoma cell line suitable for investigating CCoV. Our findings showed an increase in cell viability, with an improvement of morphological features in CCoV-infected cells at the non-toxic doses of 1 μM for VER and 0.5 μM for PS. In addition, we observed that these compounds caused a strong inhibition in the expression of the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor which is activated during CCoV infection. Our results also showed the alkalinization of lysosomes in the presence of VER or PS, which may be involved in the observed antiviral activities
Positive selection in Europeans and East-Asians at the ABCA12 gene
Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation. We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and present in non-Africans 45,000 years ago
Imaging cervical cytology with scanning near-field optical microscopy (SNOM) coupled with an IR-FEL
Cervical cancer remains a major cause of morbidity and mortality among women, especially in the developing world. Increased synthesis of proteins, lipids and nucleic acids is a pre-condition for the rapid proliferation of cancer cells. We show that scanning near-field optical microscopy, in combination with an infrared free electron laser (SNOM-IR-FEL), is able to distinguish between normal and squamous low-grade and high-grade dyskaryosis, and between normal and mixed squamous/glandular pre-invasive and adenocarcinoma cervical lesions, at designated wavelengths associated with DNA, Amide I/II and lipids. These findings evidence the promise of the SNOM-IR-FEL technique in obtaining chemical information relevant to the detection of cervical cell abnormalities and cancer diagnosis at spatial resolutions below the diffraction limit (?0.2 \ensuremathμm). We compare these results with analyses following attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy; although this latter approach has been demonstrated to detect underlying cervical atypia missed by conventional cytology, it is limited by a spatial resolution of ~3 \ensuremathμm to 30 \ensuremathμm due to the optical diffraction limit
An Ultraconserved Element Containing lncRNA Preserves Transcriptional Dynamics and Maintains ESC Self-Renewal
Ultraconserved elements (UCEs) show the peculiar feature to retain extended perfect sequence identity among human, mouse, and rat genomes. Most of them are transcribed and represent a new family of long non-coding RNAs (lncRNAs), the transcribed UCEs (T-UCEs). Despite their involvement in human cancer, the physiological role of T-UCEs is still unknown. Here, we identify a lncRNA containing the uc.170+, named T-UCstem1, and provide in vitro and in vivo evidence that it plays essential roles in embryonic stem cells (ESCs) by modulating cytoplasmic miRNA levels and preserving transcriptional dynamics. Specifically, while T-UCstem1::miR-9 cytoplasmic interplay regulates ESC proliferation by reducing miR-9 levels, nuclear T-UCstem1 maintains ESC self-renewal and transcriptional identity by stabilizing polycomb repressive complex 2 on bivalent domains. Altogether, our findings provide unprecedented evidence that T-UCEs regulate physiological cellular functions and point to an essential role of T-UCstem1 in preserving ESC identity
Temperature and force dependence of nanoscale electron transport via the Cu protein Azurin
The mechanisms of solid-state electron transport (ETp) via a monolayer of
immobilized Azurin (Az) was examined by conducting probe atomic force
microscopy (CP-AFM), both as function of temperature (248 - 373K) and of
applied tip force (6-12 nN). By varying both temperature and force in CP-AFM,
we find that the ETp mechanism can alter with a change in the force applied via
the tip to the proteins. As the applied force increases, ETp via Az changes
from temperature-independent to thermally activated at high temperatures. This
is in contrast to the Cu-depleted form of Az (apo-Az), where increasing the
applied force causes only small quantitative effects, that fit with a decrease
in electrode spacing. At low force ETp via holo-Az is temperature-independent
and thermally activated via apo-Az. This observation agrees with
macroscopic-scale measurements, thus confirming that the difference in ETp
dependence on temperature between holo- and apo-Az is an inherent one that may
reflect a difference in rigidity between the two forms. An important
implication of these results, which depend on CP-AFM measurements over a
significant temperature range, is that for ETp measurements on floppy systems,
such as proteins, the stress applied to the sample should be kept constant or,
at least controlled during measurement.Comment: 24 pages, 6 figures, plus Supporting Information with 4 pages and 2
figure
Fungal endophytes from arid areas of Andalusia: high potential sources for antifungal and antitumoral agents
Native plant communities from arid areas present distinctive characteristics to survive in extreme
conditions. The large number of poorly studied endemic plants represents a unique potential
source for the discovery of novel fungal symbionts as well as host-specific endophytes not yet
described. The addition of adsorptive polymeric resins in fungal fermentations has been seen to
promote the production of new secondary metabolites and is a tool used consistently to generate
new compounds with potential biological activities. A total of 349 fungal strains isolated from 63
selected plant species from arid ecosystems located in the southeast of the Iberian Peninsula, were
characterized morphologically as well as based on their ITS/28S ribosomal gene sequences. The fungal
community isolated was distributed among 19 orders including Basidiomycetes and Ascomycetes,
being Pleosporales the most abundant order. In total, 107 different genera were identified being
Neocamarosporium the genus most frequently isolated from these plants, followed by Preussia and
Alternaria. Strains were grown in four different media in presence and absence of selected resins to
promote chemical diversity generation of new secondary metabolites. Fermentation extracts were
evaluated, looking for new antifungal activities against plant and human fungal pathogens, as well
as, cytotoxic activities against the human liver cancer cell line HepG2. From the 349 isolates tested,
126 (36%) exhibited significant bioactivities including 58 strains with exclusive antifungal properties
and 33 strains with exclusive activity against the HepG2 hepatocellular carcinoma cell line. After LCMS
analysis, 68 known bioactive secondary metabolites could be identified as produced by 96 strains,
and 12 likely unknown compounds were found in a subset of 14 fungal endophytes. The chemical
profiles of the differential expression of induced activities were compared. As proof of concept, ten
active secondary metabolites only produced in the presence of resins were purified and identified. The
structures of three of these compounds were new and herein are elucidated.This work was supported by Fundación MEDINA and the Andalusian Government grant
RNM-7987 ‘Sustainable use of plants and their fungal parasites from arid regions of AndalucÃa for new molecules
useful for antifungals and neuroprotectors’
Lentisone, a New Phytotoxic Anthraquinone Produced by Ascochyta lentis, the Causal Agent of Ascochyta Blight in Lens culinaris
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