Synthesis and antifungal activity of ASP9726, a novel echinocandin with potent Aspergillus hyphal growth inhibition

The synthesis and antifungal activity of ASP9726, a novel echinocandin with potent Aspergillus hyphal growth inhibition and significantly improved MIC against Candida parapsilosis and echinocandin resistant-Candida is described.     

A study on in vitro glycation processes by matrix-assisted laser desorption ionization mass spectrometry

The number of glucose molecules condensed on glycated bovine serum albumin have been easily determined by means of matrix-assisted laser desorption/ionization mass spectrometry. Measurements were carried out on samples from incubation of the proteins with glucose at different concentrations (0.02 M, 0.2 M, 2 M and 5 M). A clear increase in molecular mass of BSA with respect to incubation time is detected. In contrast to what is observed with fluorescence, the plots of molecular mass increase vs. incubation time show tha occurrence of a steady state, corresponding to the complete saturation of all the protein sites against glucose. Comparison of fluorescence and molecular mass data reveals that some further reactions, different from condensation, must take place, which could be in principle either intramolecular or originated by reactivity of modified condensed gluocse moieties vs. free glucose.     

Saldanha Bay,South Africa: recovery of Gracilaria verrucosa (Gracilariales,Rhodophyta)

Since World War II the greater Saldanha Bay lagoon system, South Africa, has been an important Gracilaria producer. Two agar factories, built in the 1960's, used Gracilaria from Saldanha Bay as their raw material. In the early 1970's the industry was destroyed as a result of dredging and marine construction operations to establish a harbor in the bay for loading ore. These environmental changes destroyed stocks and prevented the previously significant beachings of the seaweed from occurring. After a few years of no or very low commercial production, the resource slowly started to recover. The size of Gracilaria drifts increased over the following eight years to approximately one-third of the original output. This trend seems to continue. Although the stocks and resultant drifts are unlikely to recover fully to their original quantity, current production is already sufficient to ensure re-establishment of a seaweed industry in Saldanha Bay. This could have considerable socio-economic impact on the area.     

How Can the Eco‐efficiency of a Region be Measured and Monitored?

The concept of eco-efficiency is commonly referred to as a business link to sustainable development. In this article, ecoefficiency is examined at a regional level as an approach to promoting the competitiveness of economic activities in the Finnish Kymenlaakso region and mitigating their harmful impacts on the environment. The aim is to develop appropriate indicators for monitoring changes in the eco-efficiency of the region. A starting point is to produce indicators for the environmental and economic dimensions of regional development and use them for measuring regional eco-efficiency. The environmental impact indicators are based on a life-cycle assessment method, producing different types of environmental impact indicators: pressure indicators (e.g., emissions of CO₂), impact category indicators (e.g., CO₂ equivalents in the case of climate change), and a total impact indicator (aggregating different impact category indicator results into a single value). Environmental impact indicators based on direct material input, total material input, and total material requirement of the Kymenlaakso region are also assessed. The economic indicators used are the gross domestic product, the value added, and the output of the main economic sectors of Kymenlaakso. In the eco-efficiency assessment, the economic and environmental impact indicators are monitored in the same graph. In a few cases eco-efficiency ratios can also be calculated (the economic indicators are divided by the environmental indicators). Output (= value added + intermediate consumption) is used as an economic indicator related to the environmental impact indicators, which also cover the upstream processes of the region's activities. In the article, we also discuss the strengths and weaknesses of using the different environmental impact indicators.     

Production of 5-hydroxymethylfurfural in ionic liquids under high fructose concentration conditions

Acid-promoted, selective production of 5-hydroxymethylfurfural (HMF) under high fructose concentration conditions was achieved in ionic liquids (ILs) at 80 °C. A HMF yield up to 97% was obtained in 8 min using 1-butyl-3-methylimidazolium chloride ([C₄mim]Cl) catalyzed with 9 mol % hydrochloric acid. More significantly, an HMF yield of 51% was observed when fructose was loaded at a high concentration of 67 wt % in [C₄mim]Cl. Water content below 15.4% in the system had little effect on HMF yield, whereas a higher water content was detrimental to both reaction rate and HMF yield. In situ NMR analysis suggested that the transformation of fructose to HMF was a highly selective reaction that proceeded through the cyclic fructofuranosyl intermediate pathway. This work increased our capacity to produce HMF, and should be valuable to facilitate cost-efficient conversion of biomass into biofuels and bio-based products.     

Neocarzinostatin abstracts a hydrogen during formation of nucleotide 5'-aldehyde on DNA

The oxidative reaction of polydeoxyadenylic-deoxythymidylic acid [poly(dA-dT)] with neocarzinostatin that produces 5'-thymidine aldehyde esterified to the 5'-end of strand breaks proceeds with hydrogen abstraction. The abstracted hydrogen is covalently bound to the non-protein component of neocarzinostatin; only a small amount (5%) is washed out into solvent. These data rule out a peroxyl radical as the primary DNA damaging species involved in the production of the 5'-aldehyde group. In contrast to earlier reports, it is demonstrated that alpha-tocopherol is not an inhibitor of the reaction.     

Pathological consequences of low atmospheric pressure stunning in broiler chickens

Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.     

The crystal structure of chorismate lyase shows a new fold and a tightly retained product.

The enzyme chorismate lyase (CL) catalyzes the removal of pyruvate from chorismate to produce 4-hydroxy benzoate (4HB) for the ubiquinone pathway. In Escherichia coli, CL is monomeric, with 164 residues. We have determined the structure of the CL product complex by crystallographic heavy-atom methods and report the structure at 1.4-A resolution for a fully active double Cys-to-Ser mutant and at 2.0-A resolution for the wild-type. The fold involves a 6-stranded antiparallel beta-sheet with no spanning helices and novel connectivity. The product is bound internally, adjacent to the sheet, with its polar groups coordinated by two main-chain amides and by the buried side-chains of Arg 76 and Glu 155. The 4HB is completely sequestered from solvent in a largely hydrophobic environment behind two helix-turn-helix loops. The extensive product binding that is observed is consistent with biochemical measurements of slow product release and 10-fold stronger binding of product than substrate. Substrate binding and kinetically rate-limiting product release apparently require the rearrangement of these active-site-covering loops. Implications for the biological function of the high product binding are considered in light of the unique cellular role of 4HB, which is produced by cytoplasmic CL but is used by the membrane-bound enzyme 4HB octaprenyltransferase.     

Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins

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