Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

Plasmon enhanced light scattering into semiconductors by aperiodic metal nanowire arrays.

Light scattering from nanostructures is an essential ingredient in several optical technologies, and experimental verification of simulations of light scattering is important. In particular, solar cells may benefit from light-trapping due to scattering. However, light that is successfully trapped in an absorbing media such as e.g. Si necessarily escapes direct detection. We present in this paper a technique for direct measurement and analysis of light scattering from nanostructures on a surface, exemplified with aperiodic patterns of Ag strips placed on a GaAs substrate. By placing the structures on the flat face of a half-cylinder, the angular distribution of light scattered into the azimuth plane can be directly detected, including directions above the critical angle that would be captured if the substrate had the form of a slab. Modelling of the scattered light by summing up contributions from each strip agrees with the experimental results to a very detailed level, both for scattering backward and into the substrate.

Update from a 12-Year Nationwide Fungemia Surveillance: Increasing Intrinsic and Acquired Resistance Causes Concern.

New data from the years 2012 to 2015 from the Danish National Fungemia Surveillance are reported, and epidemiological trends are investigated in a 12-year perspective (2004 to 2015). During 2012 to 2015, 1,900 of 1,939 (98%) fungal bloodstream isolates were included. The average incidence was 8.4/100,000 inhabitants, and this appears to represent a stabilizing trend after the increase to 10.1/100,000 in 2011. The incidence was higher in males than females (10.0 versus 6.8) and in patients above 50 years, and those changes were mainly driven by an increasing incidence among 80-to-89-year-old males (65.3/100,000 in 2014 to 2015). The proportion of Candida albicans isolates decreased from 2004 to 2015 (64.4% to 42.4%) in parallel with a doubling of the proportion of Candida glabrata isolates (16.5% to 34.6%, P < 0.0001). C. glabrata was more common among females (34.0% versus 30.4% in males). Following an increase in 2004 to 2011, the annual drug use stabilized during the last 2 to 3 years of that time period but remained higher than in other Nordic countries. This was particularly true for the fluconazole and itraconazole use in the primary health care sector, which exceeded the combined national levels of use of these compounds in each of the other Nordic countries. Fluconazole susceptibility decreased (68.5%, 65.2%, and 60.6% in 2004 to 2007, 2008 to 2011, and 2012 to 2015, respectively, P < 0.0001), and echinocandin resistance emerged in Candida (0%, 0.6%, and 1.7%, respectively, P < 0.001). Amphotericin B susceptibility remained high (98.7%). Among 16 (2.7%) echinocandin-resistant C. glabrata isolates (2012 to 2015), 13 harbored FKS mutations and 5 (31%) were multidrug resistant. The epidemiological changes and the increased incidence of intrinsic and acquired resistance emphasize the importance of continued surveillance and of strengthened focus on antifungal stewardship.

Rapid antimicrobial susceptibility testing of clinical isolates by digital time-lapse microscopy.

Rapid antimicrobial susceptibility testing (AST) is essential for early and appropriate therapy. Methods with short detection time enabling same-day treatment optimisation are highly favourable. In this study, we evaluated the potential of a digital time-lapse microscope system, the oCelloScope system, to perform rapid AST. The oCelloScope system demonstrated a very high accuracy (96% overall agreement) when determining the resistance profiles of four reference strains, nine clinical isolates, including multi-drug-resistant isolates, and three positive blood cultures. AST of clinical isolates (168 antimicrobial agent-organism combinations) demonstrated 3.6% minor, no major and 1.2% very major errors of the oCelloScope system compared to conventional susceptibility testing, as well as a rapid and correct phenotypic detection of strains with methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum ß-lactamase (ESBL) profiles. The net average time-to-result was 108 min, with 95% of the results being available within 180 min. In conclusion, this study strongly indicates that the oCelloScope system holds considerable potential as an accurate and sensitive AST method with short time-to-result, enabling same-day targeted antimicrobial therapy, facilitating antibiotic stewardship and better patient management. A full-scale validation of the oCelloScope system including more isolates is necessary to assess the impact of using it for AST.

A generalized non-local optical response theory for plasmonic nanostructures.

Metallic nanostructures exhibit a multitude of optical resonances associated with localized surface plasmon excitations. Recent observations of plasmonic phenomena at the sub-nanometre to atomic scale have stimulated the development of various sophisticated theoretical approaches for their description. Here instead we present a comparatively simple semiclassical generalized non-local optical response theory that unifies quantum pressure convection effects and induced charge diffusion kinetics, with a concomitant complex-valued generalized non-local optical response parameter. Our theory explains surprisingly well both the frequency shifts and size-dependent damping in individual metallic nanoparticles as well as the observed broadening of the crossover regime from bonding-dipole plasmons to charge-transfer plasmons in metal nanoparticle dimers, thus unravelling a classical broadening mechanism that even dominates the widely anticipated short circuiting by quantum tunnelling. We anticipate that our theory can be successfully applied in plasmonics to a wide class of conducting media, including doped semiconductors and low-dimensional materials such as graphene.

Fusarin C acts like an estrogenic agonist and stimulates breast cancer cells in vitro.

Fusarin C is a mycotoxin produced by several Fusarium species and has been associated with esophageal cancer due to its carcinogenic effects. Here, we report that fusarin C stimulates growth of the breast cancer cell line MCF-7. This suggests that fusarin C can act as an estrogenic agonist and should be classified as a mycoestrogen. MCF-7 cells were stimulated in the range between 0.1 and 20µM and inhibited when the concentration exceeded 50µM. The toxicity of fusarin C is comparable to other mycoestrogens such as zearalenone, but the chemical structure of fusarin C is very different from other known estrogen agonists. Furthermore, the toxicity of fusarin C was tested in five additional human cell lines Caco 2, U266, PC3, MDA-MB-231 and MCF-10a which were all inhibited when the concentration of fusarin C exceeded 10µM. To the best of our knowledge this is the first report on the mycoestrogenic properties of fusarin C.

A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma.

Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease activity in six heavily pretreated patients with multiple myeloma (MM). These patients were treated with simvastatin (15 mg/kg/day) for 7 days followed by a rest period of 21 days in two 4-week cycles. Endpoints were changes in the level of biochemical markers of (i) osteoclast activity (tartrate resistant acid phosphatase, TRACP); (ii) bone resorption (collagen fragments CTX and NTX); (iii) bone formation (osteocalcin and aminoterminal propeptide of type I collagen PINP); (iv) cholesterol; (v) regulators of bone metabolism [osteoprotegerin (OPG) and Dickkopf-1 (DKK-1)] and (vi) disease activity (monoclonal proteins or free light chains in serum). TRACP activity in serum and levels of collagen fragments (NTX) in urine increased for all patients temporarily during the 7 days of treatment with HD-Sim indicating that osteoclasts may have been stimulated rather than inhibited. The other markers of bone metabolism showed no change. None of the patients showed any reduction in free monoclonal light chains or monoclonal proteins in serum during treatment with HD-Sim. In spite of the fact that bone turn over effects of HD-Sim may have been blunted by concomitant treatment of patients with other drugs we observed a transient increase in markers of osteoclast activity. This sign of a transient stimulation of osteoclast activity suggests that HD-Sim may be harmful rather than beneficial for MM patients. For this reason and because of gastro-intestinal side effects the study was stopped prematurely.

Plasmon-polariton nano-strip resonators: from visible to infra-red.

Dispersion of the resonant properties exhibited by silver and gold nano-strips in a wide range of wavelengths is considered. The tunability and Q-factor of scattering resonances as well as the field enhancement achieved at strip terminations are analyzed in the wavelength range from visible to near infrared (400-1700 nm), confirming that the resonant behaviour is dominated by dispersion properties of short-range surface-plasmon polaritons (SR-SPPs) propagating along the strip. It is found that, while the Q-factor decreases for longer wavelengths due to the SR-SPP dispersion curve moving closer to the light line, the field enhancement depending also on the metal susceptibility magnitude remains largely unaffected. The results obtained are also used to estimate the phase change involved in the SR-SPP reflection by strip terminations.

Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?

A major clinical manifestation of bone cancers is bone destruction. It is widely accepted that this destruction is not caused by the malignant cells themselves, but by osteoclasts, multinucleated cells of monocytic origin that are considered to be the only cells able to degrade bone. The present study demonstrates that bone-resorbing osteoclasts from myeloma patients contain nuclei with translocated chromosomes of myeloma B-cell clone origin, in addition to nuclei without these translocations, by using combined FISH and immunohistochemistry on bone sections. These nuclei of malignant origin are transcriptionally active and appear fully integrated amongst the other nuclei. The contribution of malignant nuclei to the osteoclast population analysed in this study was greater than 30%. Osteoclast-myeloma clone hybrids contained more nuclei than normal osteoclasts and their occurrence correlated with the proximity of myeloma cells. Similar hybrid cells were generated in myeloma cell-osteoclast co-cultures, as revealed by tracing myeloma nuclei using translocations, bromo-deoxyuridine, or the Y chromosome of male myeloma cells in female osteoclasts. These observations indicate that hybrid cells can originate through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells participate directly. The possibility that malignant cells corrupt host cells by the transfer of malignant DNA may have been underestimated to date in cancer research.

Near fields and far fields generated by sources in the presence of dielectric structures with cylindrical symmetry.

A full-vectorial integral equation method is presented for calculating near fields and far fields generated by sources in the presence of general finite-sized dielectric structures with cylindrical symmetry. The method is relevant for modeling of a class of antenna designs and some optical components with cylindrical symmetry, e.g., vertical-cavity surface-emitting lasers, microdisk lasers, and light-emitting diodes.

Analysis of air-guiding photonic bandgap fibers.

We present what is to our knowledge the first theoretical analysis of air-guiding photonic bandgap fibers. The fibers are characterized by a large hollow core and a microstructured cladding exhibiting photonic bandgap effects. Using an efficient, full-vectorial numerical method, we explain the operational principle of the fibers and obtain detailed information about the properties of the air-guided modes. This information includes accurate determination of the modes' spectral extent, cutoff properties, and mode-field distributions.

Atrial septal defect, primum type. Results of surgical closure in 46 patients.

Surgical closure of an atrial septal defect of the ostium primum type was performed in 46 patients during the years 1965-78. All closures were performed with a Dacron patch and the mitral valve defect was sutured. The operative mortality was 6.5%. Pre-operatively, all patients had right bundle-branch block with left axis deviation. Severe heart block did not develop in any of the survivors. One of the patients who died had a partial atrioventricular block postoperatively. Arrhythmia developed in 5 patients, but was cardioverted to sinus rhythm. The operative technique of placing the lower sutures at the mitral valve parallel to the annulus to avoid the conduction bundle is emphasized. Repair of the tricuspid valve was performed in 10 cases and simultaneous closure of a secundum defect was made in 14. Preoperative catheterization revealed arteriovenous shunts ranging from 60 to 500% of the cardiac output. Recatheterization of 32 patients one year postoperatively showed residual shunts ranging from 20 to 75% in 5 patients who were otherwise without clinical symptoms. All survivors had a systolic apical murmur of the mitral insufficiency type.