Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the World's poorest, however vaccines are absent ...and drug therapy limited. Recently, public-private partnerships have developed to identify new modes of controlling leishmaniasis. Most of these collaborative efforts have relied upon the small molecule synthetic compound libraries held by industry, but the number of New Chemical Entities (NCE) identified and entering development as antileishmanials has been very low. In light of this, here we describe a public-private effort to identify natural products with activity against Leishmania mexicana, a causative agent of cutaneous leishmanaisis (CL). Utilising Hypha Discovery's fungal extract library which is rich in small molecule (<500 molecular weight) secondary metabolites, we undertook an iterative phenotypic screening and fractionation approach to identify potent and selective antileishmanial hits. This led to the identification of a novel oxidised bisabolane sesquiterpene which demonstrated activity in an infected cell model and was shown to disrupt multiple processes using a metabolomic approach. In addition, and importantly, this study also sets a precedent for new approaches for CL drug discovery.
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Lower mycotoxin levels in Bt maize grain Folcher, L.; Delos, M.; Marengue, E. ...
Agronomy for sustainable development,
2010/12, Letnik:
30, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Mycotoxins produced by
Fusarium
spp. during plant cultivation induce severe diseases in animal and humans. In 2007 a European Union regulation set maximum concentrations of mycotoxins in maize and ...derivatives of 4000 ppb for fumonisins B
1
and B
2
, 1750 ppb for deoxynivalenol, and 350 ppb for zearalenone. To assess the safety of French maize food, investigations are currently being carried out by the national Biological Risk Monitoring network. Here, 84 plots were cropped with the Bt maize MON 810 and its isogenic non-Bt counterpart in 2005 and 2006 in Southwestern France. Mycotoxin levels were measured in grain at harvest. Fumonisins B
1
and B
2
, deoxynivalenol, and zearalenone were analysed by liquid chromatography-mass spectrometry. The data were analysed statistically using non-parametric tests for mycotoxins and analysis of variance for weather variables. As the climate was homogenous inside the experimental area, the transgenic event introduced into the maize was the only key parameter which differed between Bt and non-Bt maize plots. Our results show that Bt maize decreased concentrations of fumonisins by 90% and zearalenone by 50%, whereas the concentration of deoxynivalenol was slightly increased. Those findings suggest a competition among
Fusarium
species that produce fumonisins or trichothecenes. According to the European regulation, 93% of the Bt maize crops can be sold, compared with only 45% for non-Bt maize plots. Our results thus show that Bt maize improved food safety by greatly reducing mycotoxin levels in field crops in Southwestern France.
The management of certain plant beneficial microorganisms biological control agents (BCAs) seems to be a promising and environmental friendly method to control plant pathogens. However, applications ...are still limited because of the lack of consistency of BCAs when they are applied in the field. In the present paper, the advantages and limitations of BCAs are seen through the example of Pythium oligandrum, an oomycete that has received much attention in the last decade. The biological control exerted by P. oligandrum is the result of a complex process, which includes direct effects through the control of pathogens and/or indirect effects mediated by P. oligandrum, i.e. induction of resistance and growth promotion. P. oligandrum antagonism is a multifaceted and target fungus-dependent process. Interestingly, it does not seem to disrupt microflora biodiversity on the roots. P. oligandrum has an atypical relationship with the plant because it rapidly penetrates into the root tissues but it cannot stay alive in planta. After root colonisation, because of the elicitation by P. oligandrum of the plant-defence system, plants are protected from a range of pathogens. The management of BCAs, here P. oligandrum, is discussed with regard to its interactions with the incredibly complex agrosystems.
Question: Can genetic tools combined with phytogeography help to define local plants and how geographically close the source population should be to the restoration site? Location: Subalpine and ...alpine French Pyrenees. Methods: The main phytogeographic boundaries in the French Pyrenees described by different authors were studied and this geographic pattern was compared with the results of genetic analysis for the four Pyrenean plants studied (Trifolium alpinum, Festuca eskia, Festuca gautieri and Rumex scutatus), based on random amplified polymorphic DNA (RAPD) marker analysis, unweighted pair-group method with arithmetic averages (UPGMA) analysis and Mantel correlograms comparing geographic and genetic distances. Results: The genetic analysis allowed definition of two main evolutionarily significant units (ESUs) for the plants under study. Although the limit between the two zones was slightly variable according to the species considered, an eastern and a western ESU was consistently observed. This delineation was concordant with the main phytogeographic boundaries of the French Pyrenees. Conclusion: RAPD markers and associated Mantel correlograms can be useful to draw ESUs for individual species when the sampling intensity is relatively dense, and similarities were revealed between species sharing the same distribution range. This delineation allowed integration of infraspecific plant variation in the management of natural resources for revegetation in the Pyrenees. Nevertheless, caution is needed for the establishment of seed pools in order to maximize genetic diversity in each of the pools during collection and production.
The purpose of this study was to develop an LC/MS assay to accurately detect three mycotoxins produced by Fusarium graminearum in various matrices. Using different LC conditions, deoxynivalenol ...(DON), 15-acetyldeoxynivalenol (15-ADON), and zearalenone (ZEN) were detected in four different matrices (fungal liquid cultures, maize grain, insect larvae and pig serum). The sensitivity of MS detection allowed us to detect concentrations as low as 8 ppb of DON and 12 ppb of ZEN. A very small quantity of matrix was therefore necessary for successful analysis of these toxins and a variety of experimental situations were successfully investigated using this technique. Production of 15-ADON and butenolide was monitored in a liquid culture of F. graminearum under controlled conditions. Using simple extraction procedures, the differential accumulation of DON and 15-ADON was followed in inoculated maize genotypes varying in susceptibility to F. graminearum. Toxicokinetic studies were carried out with maize insect pests reared continually on artificial diets containing ZEN and suggested that larvae may possess the ability to degrade ZEN. Finally, persistence of DON was assessed in pigs fed diet supplemented with DON, results indicated that DON accumulates quickly in pig blood and then levels decline progressively for 12 hours thereafter. The LC/MS study reported here is very useful and flexible for the detection of these mycotoxins in different media and at very low concentrations.
ABSTRACT The relationship between the primary cell wall phenolic acids, dehydrodimers of ferulic acid, and maize grain resistance to Fusarium graminearum, the causal agent of gibberella ear rot, was ...investigated. Concentrations of dehydrodimers of ferulic acid were determined in the pericarp and aleurone tissues of five inbreds and two hybrids of varying susceptibility and in a segregating population from a cross between a resistant and susceptible inbred. Significant negative correlations were found between disease severity and diferulic acid content. Even stronger correlations were observed between diferulic acid and the fungal steroid ergosterol, which is an indicator of fungal biomass in infected plant tissue. These results were consistent over two consecutive field seasons, which differed significantly for temperature and rainfall during pollination, the most susceptible stage of ear development. No correlation was found between the levels of these phenolics and deoxynivalenol levels. This is the first report of in vivo evidence that the dehydrodimers of ferulic acid content in pericarp and aleurone tissues may play a role in genotypic resistance of maize to gibberella ear rot.
Human BAHD1 promotes heterochromatic gene silencing Bierne, Hélène; Tham, To Nam; Batsche, Eric ...
Proceedings of the National Academy of Sciences - PNAS,
08/2009, Letnik:
106, Številka:
33
Journal Article
Recenzirano
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Gene silencing via heterochromatin formation plays a major role in cell differentiation and maintenance of homeostasis. Here we report the identification and characterization of a novel ...heterochromatinization factor in vertebrates, bromo adjacent homology domain-containing protein 1 (BAHD1). This nuclear protein interacts with HP1, MBD1, HDAC5, and several transcription factors. Through electron and immunofluorescence microscopy studies, we show that BAHD1 overexpression directs HP1 to specific nuclear sites and promotes the formation of large heterochromatic domains, which lack acetyl histone H4 and are enriched in H3 trimethylated at lysine 27 (H3K27me3). Furthermore, ectopically expressed BAHD1 colocalizes with the heterochromatic inactive X chromosome (Xi). The BAH domain is required for BAHD1 colocalization with H3K27me3, but not with the Xi chromosome. As highlighted by whole genome microarray analysis of BAHD1 knockdown cells, BAHD1 represses several proliferation and survival genes, in particular the insulin-like growth factor II gene (IGF2). When overexpressed, BAHD1 specifically binds the CpG-rich P3 promoter of IGF2, which increases MBD1 and HDAC5 targeting at this locus. This region contains DNA-binding sequences for the transcription factor SP1, with which BAHD1 coimmunoprecipitates. Collectively, these findings provide evidence that BAHD1 acts as a silencer by recruiting at specific promoters a set of proteins that coordinate heterochromatin assembly.
Abstract
Botanicals have been in use for a long time for pest control. A product of species coevolution, these compounds offer many environmental advantages. However, their uses during the 20th ...century have been rather marginal compared with other biocontrol methods of pests and pathogens. Improvement in our understanding of plant allelochemical mechanisms of activity offer new prospects for using these substances in crop protection. We examine the reasons behind their limited use and the actual crop protection developments involving plant allelochemicals, namely: (i) formulations including biopesticides of plant origin for organic or traditional agricultures, and (ii) improvement of plant resistance to pathogens through identification of genes coding for allelochemicals and stimulation of natural passive and active defenses of the plant. Commercial and regulatory aspects are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The kinetic behaviour of bovine erythrocyte Cu‐‐Zn SOD was investigated in Sprague Dawley male rats after subcutaneous and oral administrations of doses ranging from 0·5 to 20 mg kg−1. Studies have ...been carried out with SOD and SOD encapsulated into liposomes containing or not containing ceramides. The maximum concentration (Cmax) in blood cell pellets ranged from 8·65 to 11·03 U/mg haemoglobin (Hb) after subcutaneous injection, and from 4·48 to 8·23 U/mg Hb after oral administration. The maximum concentrations were reached in 5 h (t max) for the two routes. Comparison between the areas under the curves (AUCs) obtained after subcutaneous and oral administration allowed the calculation of relative bioavailability (F ′). The maximum bioavailability after oral administration was 14% for free SOD, 22% for SOD encapsulated into liposomes, and 57% when ceramides were added to liposomes.
Poor SOD bioavailability was enhanced by liposome encapsulation, and ceramide addition seemed to be beneficial for oral encapsulated SOD administration.
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