Changes of intraocular pressure in patients with open-angle glaucoma in relation to the passage of atmospheric fronts and environmental contamination

Effects of atmospheric frontal passages on intraocular pressure (IOP) in patients with open-angle glaucoma are statistically investigated to show the meteorotropism of this disease. Changes in IOP caused by frontal passages are evident; the response is not identical in all the patients near the day of the passage of a warm front, while on the third day following the passage of the front a well pronounced drop in IOP occurs. Anomalous increases of IOP over several months' duration occurred in the years 1986–7. This finding is explained in relation to the hypothesis of environmental contamination in Central Europe by radioactive cesium nuclides due to the Chernobyl accident.     

Engineering high α‐amylase levels in wheat grain lowers Falling Number but improves baking properties

Late maturity α‐amylase (LMA) and preharvest sprouting (PHS) are genetic defects in wheat. They are both characterized by the expression of specific isoforms of α‐amylase in particular genotypes in the grain prior to harvest. The enhanced expression of α‐amylase in both LMA and PHS results in a reduction in Falling Number (FN), a test of gel viscosity, and subsequent downgrading of the grain, along with a reduced price for growers. The FN test is unable to distinguish between LMA and PHS; thus, both defects are treated similarly when grain is traded. However, in PHS‐affected grains, proteases and other degradative process are activated, and this has been shown to have a negative impact on end product quality. No studies have been conducted to determine whether LMA is detrimental to end product quality. This work demonstrated that wheat in which an isoform α‐amylase (TaAmy3) was overexpressed in the endosperm of developing grain to levels of up to 100‐fold higher than the wild‐type resulted in low FN similar to those seen in LMA‐ or PHS‐affected grains. This increase had no detrimental effect on starch structure, flour composition and enhanced baking quality, in small‐scale 10‐g baking tests. In these small‐scale tests, overexpression of TaAmy3 led to increased loaf volume and Maillard‐related browning to levels higher than those in control flours when baking improver was added. These findings raise questions as to the validity of the assumption that (i) LMA is detrimental to end product quality and (ii) a low FN is always indicative of a reduction in quality. This work suggests the need for a better understanding of the impact of elevated expression of specific α‐amylase on end product quality.     

High‐Voltage Photogeneration Exclusively via Aggregation‐Induced Triplet States in a Heavy‐Atom‐Free Nonplanar Organic Semiconductor

The electron–hole recombination kinetics of organic photovoltaics (OPVs) are known to be sensitive to the relative energies of triplet and charge‐transfer (CT) states. Yet, the role of exciton spin in systems having CT states above 1.7 eV—like those in near‐ultraviolet‐harvesting OPVs—has largely not been investigated. Here, aggregation‐induced room‐temperature intersystem crossing (ISC) to facilitate exciton harvesting in OPVs having CT states as high as 2.3 eV and open‐circuit voltages exceeding 1.6 V is reported. Triplet excimers from energy‐band splitting result in ultrafast CT and charge separation with nonradiative energy losses of <250 meV, suggesting that a 0.1 eV driving force is sufficient for charge separation, with entropic gain via CT state delocalization being the main driver for exciton dissociation and generation of free charges. This finding can inform engineering of next‐generation active materials and films for near‐ultraviolet OPVs with open‐circuit voltages exceeding 2 V. Contrary to general belief, this work reveals that exclusive and efficient ISC need not require heavy‐atom‐containing active materials. Molecular aggregation through thin‐film processing provides an alternative route to accessing 100% triplet states on photoexcitation.     

A Synergetic Screening Approach with Companion Effector for Combination Therapy: Application to Retinoblastoma

For many cancers, the lack of potency and the toxicity of current drugs limits the dose achievable in patients and the efficacy of treatment. Among them, retinoblastoma is a rare cancer of the eye for which better chemotherapeutic options are needed. Combination therapy is a compelling approach to enhance the efficacy of current treatment, however clinical trials to test rationally designed combinations of approved drugs are slow and expensive, and limited by our lack of in-depth knowledge of drug specificity. Since many patients already turn to nutraceuticals in hopes of improving their condition, we hypothesized that certain approved drugs could potentially synergize with widely consumed supplements. Following this hypothesis, we devised an alternative screening strategy aimed at taking advantage of a bait compound such as a nutraceutical with potential therapeutic benefits but low potency, by screening chemical libraries for approved drugs that synergize with this companion effector. As a proof of concept, we sought to identify approved drugs with synergetic therapeutic effects toward retinoblastoma cells in combination with the antioxidant resveratrol, popular as a supplement. We systematically tested FDA-approved drugs and known bioactives seeking to identify such pairs, which led to uncovering only a few additive combinations; but to our surprise, we identified a class of anticancer drugs widely used in the clinic whose therapeutic effect is antagonized with resveratrol. Our observations could explain in part why some patients do not respond well to treatment. Our results validate this alternative approach, and we expect that our companion effector strategy could significantly impact both drug discovery and the nutraceutical industry.     

Potential of ligninolytic enzymatic complex produced by white‐rot fungi from genus Trametes isolated from Bulgarian forest soil

Because of the crucial role of ligninolytic enzymes in a variety of industrial processes, the demand for a new effective producer has been constantly increasing. Furthermore, information on enzyme synthesis by autochthonous fungal strains is very seldom found. Two fungal strains producing ligninolytic enzymes were isolated from Bulgarian forest soil. They were identified as being Trametes trogii and T. hirsuta. These two strains were assessed for their enzyme activities, laccase (Lac), lignin peroxidase (LiP) and Mn‐dependent peroxidase (MnP) in culture filtrate depending on the temperature and the type of nutrient medium. T. trogii was selected as the better producer of ligninolytic enzymes. The production process was further improved by optimizing a number of parameters such as incubation time, type of cultivation, volume ratio of medium/air, inoculum size and the addition of inducers. The maximum activities of enzymes synthesized by T. trogii was detected as 11100 U/L for Lac, 2.5 U/L for LiP and 4.5 U/L for MnP after 14 days of incubation at 25°C under static conditions, volume ratio of medium/air 1:6, and 3 plugs as inoculum. Among the supplements tested, 5% glycerol increased Lac activity to a significant extent. The addition of 1% veratryl alcohol had a positive effect on MnP.     

Effect of copper ions on the ligninolytic enzyme complex and the antioxidant enzyme activity in the white-rot fungus Trametes trogii 46

White-rot fungi of the Phylum Basidiomycota are quite promising in ligninolytic enzyme production and the optimization of their synthesis is of particular significance. The aim of this study was to investigate the effect of enhanced concentration of copper (Cu) ions (25–1000 μg/ml) on the activity of the ligninolytic enzyme complex (laccase, Lac; lignin peroxidase, LiP; Mn-peroxidase, MnP) in Trametes trogii 4₆, as well as the changes in the antioxidant cell response. All concentrations tested reduced significantly in growth and glucose consumption. Cu ions affected the ligninolytic enzyme activity in a dose dependent manner. Concentrations in the range of 25–100 μg/ml strongly stimulated Lac production (a 5–6-fold increase compared to the control). LiP activity was also induced by Cu, with the peak value being recorded following exposure to 50 μg/ml metal ions. In contrast, the addition of Cu ions had a positive effect on MnP activity at a concentration higher than 100 μg/ml. The maximum enzyme level was achieved at 1000 μg/ml. The results obtained on superoxide dismutase and catalase activities indicated that exposure of T. trogii 4₆ mycelia to Cu ions promoted oxidative stress. Both enzyme activities were co-ordinately produced with Lac and LiP but not co-ordinately with MnP.     

Development of Real-Time PCR Methods for the Detection of Bacterial Meningitis Pathogens without DNA Extraction

Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are the lead causes of bacterial meningitis. Detection of these pathogens from clinical specimens using traditional real-time PCR (rt-PCR) requires DNA extraction to remove the PCR inhibitors prior to testing, which is time consuming and labor intensive. In this study, five species-specific (Nm-sodC and -ctrA, Hi-hpd#1 and -hpd#3 and Sp-lytA) and six serogroup-specific rt-PCR tests (A, B, C, W, X, Y) targeting Nm capsular genes were evaluated in the two direct rt-PCR methods using PerfeCTa and 5x Omni that do not require DNA extraction. The sensitivity and specify of the two direct rt-PCR methods were compared to TaqMan traditional rt-PCR, the current standard rt-PCR method for the detection of meningitis pathogens. The LLD for all 11 rt-PCR tests ranged from 6,227 to 272,229 CFU/ml for TaqMan, 1,824–135,982 for 5x Omni, and 168–6,836 CFU/ml for PerfeCTa. The diagnostic sensitivity using TaqMan ranged from 89.2%-99.6%, except for NmB-csb, which was 69.7%. For 5x Omni, the sensitivity varied from 67.1% to 99.8%, with three tests below 90%. The sensitivity of these tests using PerfeCTa varied from 89.4% to 99.8%. The specificity ranges of the 11 tests were 98.0–99.9%, 97.5–99.9%, and 92.9–99.9% for TaqMan, 5x Omni, and PerfeCTa, respectively. PerfeCTa direct rt-PCR demonstrated similar or better sensitivity compared to 5x Omni direct rt-PCR or TaqMan traditional rt-PCR. Since the direct rt-PCR method does not require DNA extraction, it reduces the time and cost for processing CSF specimens, increases testing throughput, decreases the risk of cross-contamination, and conserves precious CSF. The direct rt-PCR method will be beneficial to laboratories with high testing volume.