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Search Results: 1 - 10 of 1664 matches for " Charlotte Held Gotfredsen "
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Comparative Chemistry of Aspergillus oryzae (RIB40) and A. flavus (NRRL 3357)
Christian Rank,Marie Louise Klejnstrup,Lene Maj Petersen,Sara Kildgaard,Jens Christian Frisvad,Charlotte Held Gotfredsen,Thomas Ostenfeld Larsen
Metabolites , 2012, DOI: 10.3390/metabo2010039
Abstract: Aspergillus oryzae and A. flavus are important species in industrial biotechnology and food safety and have been some of the first aspergilli to be fully genome sequenced. Bioinformatic analysis has revealed 99.5% gene homology between the two species pointing towards a large coherence in the secondary metabolite production. In this study we report on the first comparison of secondary metabolite production between the full genome sequenced strains of A. oryzae (RIB40) and A. flavus (NRRL 3357). Surprisingly, the overall chemical profiles of the two strains were mostly very different across 15 growth conditions. Contrary to previous studies we found the aflatrem precursor 13-desoxypaxilline to be a major metabolite from A. oryzae under certain growth conditions. For the first time, we additionally report A. oryzae to produce parasiticolide A and two new analogues hereof, along with four new alkaloids related to the A. flavus metabolites ditryptophenalines and miyakamides. Generally the secondary metabolite capability of A. oryzae presents several novel end products likely to result from the domestication process from A. flavus.
Bio-Activity and Dereplication-Based Discovery of Ophiobolins and Other Fungal Secondary Metabolites Targeting Leukemia Cells
Tanja Thorskov Bladt,Claudia Dürr,Peter Boldsen Knudsen,Sara Kildgaard,Jens Christian Frisvad,Charlotte Held Gotfredsen,Martina Seiffert,Thomas Ostenfeld Larsen
Molecules , 2013, DOI: 10.3390/molecules181214629
Abstract: The purpose of this study was to identify and characterize fungal natural products (NPs) with in vitro bioactivity towards leukemia cells. We based our screening on a combined analytical and bio-guided approach of LC-DAD-HRMS dereplication, explorative solid-phase extraction (E-SPE), and a co-culture platform of CLL and stromal cells. A total of 289 fungal extracts were screened and we tracked the activity to single compounds in seven of the most active extracts. The novel ophiobolin U was isolated together with the known ophiobolins C, H, K as well as 6-epiophiobolins G, K and N from three fungal strains in the Aspergillus section Usti. Ophiobolins A, B, C and K displayed bioactivity towards leukemia cells with induction of apoptosis at nanomolar concentrations. The remaining ophiobolins were mainly inactive or only slightly active at micromolar concentrations. Dereplication of those ophiobolin derivatives possessing different activity in combination with structural analysis allowed a correlation of the chemical structure and conformation with the extent of bioactivity, identifying the hydroxy group at C3 and an aldehyde at C21, as well as the A/B- cis ring structure, as indispensible for the strong activity of the ophiobolins. The known compounds penicillic acid, viridicatumtoxin, calbistrin A, brefeldin A, emestrin A, and neosolaniol monoacetate were identified from the extracts and also found generally cytotoxic.
Aspergillus nidulans Synthesize Insect Juvenile Hormones upon Expression of a Heterologous Regulatory Protein and in Response to Grazing by Drosophila melanogaster Larvae
Morten Thrane Nielsen, Marie Louise Klejnstrup, Marko Rohlfs, Diana Chinyere Anyaogu, Jakob Bl?sbjerg Nielsen, Charlotte Held Gotfredsen, Mikael R?rdam Andersen, Bjarne Gram Hansen, Uffe Hasbro Mortensen, Thomas Ostenfeld Larsen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073369
Abstract: Secondary metabolites are known to serve a wide range of specialized functions including communication, developmental control and defense. Genome sequencing of several fungal model species revealed that the majority of predicted secondary metabolite related genes are silent in laboratory strains, indicating that fungal secondary metabolites remain an underexplored resource of bioactive molecules. In this study, we combine heterologous expression of regulatory proteins in Aspergillus nidulans with systematic variation of growth conditions and observe induced synthesis of insect juvenile hormone-III and methyl farnesoate. Both compounds are sesquiterpenes belonging to the juvenile hormone class. Juvenile hormones regulate developmental and metabolic processes in insects and crustaceans, but have not previously been reported as fungal metabolites. We found that feeding by Drosophila melanogaster larvae induced synthesis of juvenile hormone in A. nidulans indicating a possible role of juvenile hormone biosynthesis in affecting fungal-insect antagonisms.
Antibacterial Compounds from Marine Vibrionaceae Isolated on a Global Expedition
Matthias Wietz,Maria Mansson,Charlotte H. Gotfredsen,Thomas O. Larsen,Lone Gram
Marine Drugs , 2010, DOI: 10.3390/md8122946
Abstract: On a global research expedition, over 500 bacterial strains inhibitory towards pathogenic bacteria were isolated. Three hundred of the antibacterial strains were assigned to the Vibrionaceae family. The purpose of the present study was to investigate the phylogeny and bioactivity of five Vibrionaceae strains with pronounced antibacterial activity. These were identified as Vibrio coralliilyticus (two strains), V. neptunius (two?strains), and Photobacterium halotolerans (one strain) on the basis of housekeeping gene sequences. The two related V. coralliilyticus and V. neptunius strains were isolated from distant oceanic regions. Chemotyping by LC-UV/MS underlined genetic relationships by showing highly similar metabolite profiles for each of the two V. coralliilyticus and V.?neptunius strains, respectively, but a unique profile for P. halotolerans. Bioassay-guided fractionation identified two known antibiotics as being responsible for the antibacterial activity; andrimid (from V. coralliilyticus) and holomycin (from P. halotolerans). Despite the isolation of already known antibiotics, our findings show that marine Vibrionaceae are a resource of antibacterial compounds and may have potential for future natural product discovery.
Identification of Four New agr Quorum Sensing-Interfering Cyclodepsipeptides from a Marine Photobacterium
Louise Kjaerulff,Anita Nielsen,Maria Mansson,Lone Gram,Thomas O. Larsen,Hanne Ingmer,Charlotte H. Gotfredsen
Marine Drugs , 2013, DOI: 10.3390/md11125051
Abstract: During our search for new natural products from the marine environment, we discovered a wide range of cyclic peptides from a marine Photobacterium, closely related to P. halotolerans. The chemical fingerprint of the bacterium showed primarily non-ribosomal peptide synthetase (NRPS)-like compounds, including the known pyrrothine antibiotic holomycin and a wide range of peptides, from diketopiperazines to cyclodepsipeptides of 500–900 Da. Purification of components from the pellet fraction led to the isolation and structure elucidation of four new cyclodepsipeptides, ngercheumicin F, G, H, and I. The ngercheumicins interfered with expression of virulence genes known to be controlled by the agr quorum sensing system of Staphylococcus aureus, although to a lesser extent than the previously described solonamides from the same strain of Photobacterium.
Inhibition of Virulence Gene Expression in Staphylococcus?aureus by Novel Depsipeptides from a Marine Photobacterium
Maria Mansson,Anita Nielsen,Louise Kj?rulff,Charlotte H. Gotfredsen,Matthias Wietz,Hanne Ingmer,Lone Gram,Thomas O. Larsen
Marine Drugs , 2011, DOI: 10.3390/md9122537
Abstract: During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of ag r. A marine Photobacterium produced compounds interfering with agr in S.?aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium.
爆轰波的拐角效应(英)
Held
含能材料 , 2000,
Abstract: 爆轰波绕过急拐角或弧形拐角会产生不同的波形,其冲击波速度或爆速是相同的,但爆压却不同,这可以从不同的发光强度看出,爆轰波绕过急拐角后的光输出弱于绕过弧形拐角的发射光强度,显然这也是由于压力不同引起的。
StreamofReactionProductsbehindtheDetonationWaveFront
Held
含能材料 , 2001,
Abstract:
用简单方法测定爆轰序列时间差(英)
Held
含能材料 , 2000,
Abstract: 同步起爆装置的时间差、包括不同雷管的起爆时间差、传爆药爆轰波成长的时间差以及爆轰波最后到达主炸药的时间差,可通过印在柔性圆盘钢靶板上的道氏沟槽线的距离来测量,测量误差小于0.1μs.
Increased susceptibility to cardiovascular effects of dihydrocapcaicin in resuscitated rats. Cardiovascular effects of dihydrocapsaicin
Keld Fosgerau, Giuseppe Ristagno, Magdalena Jayatissa, Mads Axelsen, Jacob W Gotfredsen, Uno J Weber, Lars K?ber, Christian Torp-Pedersen, Charlotte Videbaek
BMC Cardiovascular Disorders , 2010, DOI: 10.1186/1471-2261-10-39
Abstract: Here we tested the hypothesis that the cardiovascular system in healthy rats and rats resuscitated from a cardiac arrest may be differentially affected by a transient receptor potential vanilloid type 1 agonist, by continuous intravenous infusion of dihydrocapsaicin (DHC).Compared to baseline, infusion of DHC caused an initial increase in mean arterial blood pressure in both healthy and resuscitated rats of 25% and 10%, respectively. Also, we observed an initial response of tachycardia in both healthy and resuscitated rats of 30% and 20%, respectively. Then, at high levels of DHC infusion (> 2.0 mg/kg/hr) we observed two single episodes of transient bradycardia and hypotension in 33% of the healthy rats, which was consistent with a TRPV1 agonist induced Bezold-Jarisch reflex. In contrast, in resuscitated rats we observed multiple episodes of bradycardia/hypotension in 100% of the rats and at a dose of DHC of 0.65 mg/kg/hr. Notably, this DHC effect could be completely blocked in the resuscitated rats by pre-treatment with atropine, a muscarinic acetylcholine antagonist.Our results indicate that the susceptibility of the rats towards TRPV1 agonist induced Bezold-Jarisch reflex is increased in those resuscitated from cardiac arrest compared to the healthy situation.The transient receptor potential vanilloid type 1 (TRPV1) is a member of the mammalian transient receptor potential family of ion channels [1] and was cloned in 1997 [2]. TRPV1 is a non-selective cation channel with a preference for calcium, which can be directly activated by noxious heat (> 43°C), extracellular acidification, as well as a large heterogeneous group of natural compounds such as dihydrocapsaicin (DHC) from chili pepper [3,4]. The TRPV1 receptor is widely expressed in the human body [5,6] particularly in "port-of-entry" tissues, the central nervous system (CNS), and in the peripheral nervous system in primary small to medium diameter sensory neurons such as dorsal root, trigeminal, and nodose g
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