Discrepancies between MIC and MLC values of amphotericin B against isolates ofAspergillus species

There is little information addressing the phenomena of discrepancy between minimal inhibitory concentrations (MIC) and minimal lethal concentrations (MLC) values of amphotericin B (AMB) to clinical isolates of fungi. This study assessed in vitro activity of AMB against 70 clinical isolates of aspergilli: 30 strains ofAspergillus fumigatus, 20 strains ofAspergillus flavus and 20 strains ofAspergillus niger. Susceptibility tests were accomplished using a macro broth dilution procedure, with special emphasis on ascertainment of MLCs. AMB exhibited low MIC values against all clinical isolates. While we did not identify any AMB resistant isolates among 70Aspergillus spp. studied as judged by MIC levels, analysis of the data demonstrated a clear discrepancy between the MIC and MLC levels of AMB obtained against clinical isolates ofAspergillus spp. The MLC values of AMB were significantly higher than the MIC values with MIC 50 and MIC 90 of 0.29 and 0.5 µg/ml, respectively, at the second reading time, and MLC 50 and MLC 90 of 2.31 and 9.24 µg/ml, respectively (p<0.001). Additionally, minimal lethal concentrations in 36/70 (51%) of aspergillal isolates studied produced drug concentrations above those which can usually be sustained in patient plasma or tissue.     

Improving lower limb weight distribution asymmetry during the squat using Nintendo Wii Balance Boards and real-time feedback

Weight-bearing asymmetry (WBA) may be detrimental to performance and could increase the risk of injury; however, detecting and reducing it is difficult in a field setting. This study assessed whether a portable and simple-to-use system designed with multiple Nintendo Wii Balance Boards (NWBBs) and customized software can be used to evaluate and improve WBA. Fifteen elite Australian Rules Footballers and 32 age-matched, untrained participants were tested for measures of WBA while squatting. The NWBB and customized software provided real-time visual feedback of WBA during half of the trials. Outcome measures included the mean mass difference (MMD) between limbs, interlimb symmetry index (SI), and percentage of time spent favoring a single limb (TFSL). Significant reductions in MMD (p = 0.028) and SI (p = 0.007) with visual feedback were observed for the entire group data. Subgroup analysis revealed significant reductions in MMD (p = 0.047) and SI (p = 0.026) with visual feedback in the untrained sample; however, the reductions in the trained sample were nonsignificant. The trained group showed significantly less WBA for TFSL under both visual conditions (no feedback: p = 0.015, feedback: p = 0.017). Correlation analysis revealed that participants with high levels of WBA had the greatest response to feedback (p < 0.001, ρ = 0.557). In conclusion, WBA exists in healthy untrained adults, and these asymmetries can be reduced using real-time visual feedback provided by an NWBB-based system. Healthy, well-trained professional athletes do not possess the same magnitude of WBA. Inexpensive, portable, and widely available gaming technology may be used to evaluate and improve WBA in clinical and sporting settings.     

Purification and characterization of Dolichos lablab lectin

The mannose/glucose-binding Dolichos lablab lectin (designated DLL) has been purified from seeds of Dolichos lablab (hyacinth bean) to electrophoretic homogeneity by affinity chromatography on an ovalbumin- Sepharose 4B column. The purified lectin gave a single symmetric protein peak with an apparent molecular mass of 67 kDa on gel filtration chromatography, and five bands ranging from 10 kDa to 22 kDa upon SDS-PAGE. N-Terminal sequence analysis of these bands revealed subunit heterogeneity due to posttranslational proteolytic truncation at different sites mostly at the carboxyl terminus. The carbohydrate binding properties of the purified lectin were investigated by three different approaches: hemagglutination inhibition assay, quantitative precipitation inhibition assay, and ELISA. On the basis of these studies, it is concluded that the Dolichos lablab lectin has neither an extended carbohydrate combining site, nor a hydrophobic binding site adjacent to it. The carbohydrate combining site of DLL appears to most effectively accommodate a nonreducing terminal alpha-d-mannosyl unit, and to be complementary to the C-3, C-4, and C-6 equatorial hydroxyl groups of alpha-d-mannopyranosyl and alpha-d-glucopyranosyl residues. DLL strongly precipitates murine IgM but not IgG, and the recent finding that this lectin interacts specifically with NIH 3T3 fibroblasts transfected with the Flt3 tyrosine kinase receptor and preserves human cord blood stem cells and progenitors in a quiescent state for prolonged periods in culture, make this lectin a valuable tool in biomedical research.      

Putting a new twist on actin: ADF/cofilins modulate actin dynamics.

The actin-depolymerizing factor (ADF)/cofilins are a family of essential actin regulatory proteins, ubiquitous among eukaryotes, that enhance the turnover of actin by regulating the rate constants of polymerization and depolymerization at filament ends, changing the twist of the filament and severing actin filaments. Genetic and cell-biological studies have shown that an ADF/cofilin is required to drive the high turnover of the actin cytoskeleton observed in vivo. The activity of ADF/cofilin is regulated by a variety of mechanisms, including specific phosphorylation and dephosphorylation. This review addresses aspects of ADF/cofilin structure, dynamics, regulation and function.     

ADF/cofilin weakens lateral contacts in the actin filament.

Observed in vivo motility rates can only be accounted for if the rate of actin filament treadmilling in cells is considerably greater than has been quantified for purified actin in vitro. ADF/cofilin is uniquely suited to promote actin dynamics in cells, owing to its remarkable ability to change actin filament structure. In earlier work we showed that human cofilin chanRges filament twist by about 5 degrees per subunit and suggested that this contributes to increased filament turnover. Our initial structural modeling provided some insights into how the longitudinal actin-actin contacts might be disrupted following cofilin-induced twisting. Here we present direct evidence that cofilin also disrupts lateral actin-actin contacts in the filament and suggest a model showing how this could contribute to cofilin's novel effects on actin filament dynamics and assembly.     

不同胁迫预处理提高水稻幼苗抗寒性期间蛋白质的变化

水稻(Oryza sativa L.)幼苗经盐、热激和冷三种不同胁迫预处理均提高了幼苗的抗寒性。与未预处理苗相比,在处理后、低温伤害后和常温下恢复2d的三个时期,不同胁迫预处理苗的可溶性和热不稳定蛋白含量变化趋势甚为相似,但热稳定蛋白含量变化则各有异同。SDS-PAGE图谱分析显示,不同胁迫预处理提高水稻幼苗抗寒性时,其可溶性蛋白、热稳定和热不稳定蛋白组成变化亦各有异同。除诱导出共有的新多肽外,还各自诱导出特有的新多肽。结果表明,植物对不同胁迫的交叉适应存在一定的共同机理,但亦可看出植物对同一种环境胁迫似乎不是以同一的机理去适应。     

Coordination of phage genome degradation versus host genome protection by a bifunctional restriction-modification enzyme visualized by CryoEM

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Cradle-to-gate life cycle assessment of global manganese alloy production

Purpose

Manganese is a metal used extensively in everyday life, particularly in structural steel. Despite the importance of manganese as an essential alloying element in steel and stainless steel, the environmental profile of manganese alloys lacked globally representative, primary industry data. The International Manganese Institute (IMnI) and Hatch completed the first global life cycle assessment (LCA) of manganese alloy production, providing environmental benchmarks and a firm foundation of accurate data with which to inform other industry-led initiatives.

Methods

The study compiled primary data from 16 ore and alloy producers worldwide, covering 18 % of global ore production and 8 % of global alloy production for 2010. This peer-reviewed, ISO 14040 compliant LCA covers the cradle-to-gate life cycles of silicomanganese, ferromanganese, and refined ferromanganese. The study provides a comprehensive picture of global environmental performance, quantifying energy consumption, global warming potential (GWP), acidification potential (AP), photochemical ozone creation potential (POCP), primary water use, and primary waste generation. A novel model architecture was devised to generate process, site, and cradle-to-gate LCAs for single and multiple sites simultaneously, extracting greater value from the LCA process by facilitating environmental and operational benchmarking within the industry.

Results and discussion

The results of the study show that total GWP, AP, and POCP for 1 kg of average manganese alloy was 6.0 kg CO₂e, 45 g SO₂e, and 3 g C₂H₄e, respectively. Electricity demand and coal and coke consumption during smelting are the dominant operating parameters contributing to environmental performance. On-site air emission measures (GWP, POCP, NO_X, and particulate matter (PM)) contributed 25 to 35 % of total life cycle emissions. Overburden and waste rock were the most significant primary solid waste flows by mass. The study provides a resource for improvement at the global industry and site scales by establishing benchmarks, identifying hotspots, and quantifying the benefits of efficiency savings through process optimization.

Conclusions

This LCA provides accurate primary data to improve steel and stainless steel product LCAs and communicate the environmental performance of the industry in quantitative terms. It facilitates dialogue between manganese producers and consumers through a shared understanding of the environmental profile of the industry. Through leveraging the study to identify hotspots within the manganese supply chain, producers can work both independently and collectively towards improving the environmental and economic performance of manganese alloys.