New,Non‐quinone Fluorogeldanamycin Derivatives Strongly Inhibit Hsp90

Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA‐blocked mutant with all possible monofluoro 3‐aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies.     

Characterization of copper bioreduction and biosorption by a highly copper resistant bacterium isolated from copper-contaminated vineyard soil

Copper is an essential but toxic heavy metal that negatively impacts living systems at high concentration. This study presents factors affecting copper bioremoval (bioreduction and biosorption) by a highly copper resistant monoculture of Pseudomonas sp. NA and copper bioremoval from soil. Seven bacteria resistant to high concentration of Cu(II) were isolated from enrichment cultures of vineyard soils and mining wastes. Culture parameters influencing copper bioreduction and biosorption by one monoculture isolate were studied. The isolate was identified by 16S rRNA gene sequence analysis as a Pseudomonas sp. NA (98% similarity to Pseudomonas putida, Pseudomonas plecoglossicida and other Pseudomonas sp.). The optimal temperature for growth was 30 °C and bioremoval of Cu(II) was maximal at 35 °C. Considerable growth of the isolate was observed between pH 5.0 and 8.0 with the highest growth and biosorption recorded at pH 6.0. Maximal bioreduction was observed at pH 5.0. Cu(II) bioremoval was directly proportional to Cu(II) concentration in media. Pseudomonas sp. NA removed more than 110 mg L^− 1 Cu(II) in water within 24 h through bioreduction and biosorption at initial concentration of 300 mg L^− 1. In cultures amended with 100 mg L^− 1, 20.7 mg L^− 1 of Cu(II) was biologically reduced and more than 23 mg L^− 1 of Cu(II) was biologically removed in 12 h. The isolate strongly promoted copper bioleaching in soil. Results indicate that Pseudomonas sp. NA has good potential as an agent for removing copper from water and soil.     

Heavy metal exposure in patients suffering from electromagnetic hypersensitivity

Background

Risks from electromagnetic devices are of considerable concern. Electrohypersensitive (EHS) persons attribute a variety of rather unspecific symptoms to the exposure to electromagnetic fields. The pathophysiology of EHS is unknown and therapy remains a challenge.

Objectives

Heavy metal load has been discussed as a potential factor in the symptomatology of EHS patients. The main objective of the study was to test the hypothesis of a link between EHS and heavy metal exposure.

Methods

We measured lead, mercury and cadmium concentrations in the blood of 132 patients (n = 42 males and n = 90 females) and 101 controls (n = 34 males and n = 67 females).

Results

Our results show that heavy metal load is of no concern in most cases of EHS but might play a role in exceptional cases.

Conclusions

The data do not support the general advice to heavy metal detoxification in EHS.     

Release to the gas phase of metals, S and Cl during combustion of dedicated waste fractions

The release to the gas phase of inorganic elements such as alkali metals, Cl, S, and heavy metals in Waste-to-Energy (WtE) boilers is a challenge. Besides the risk of harmful emissions to the environment, inorganic elements released from the grate may cause severe ash deposition and corrosion problems in the boiler, subsequently leading to decreased overall efficiency and costly, unscheduled shut-downs. The objective of this study was to obtain quantitative data on the release of inorganic elements from dedicated, well-characterized waste fractions; in order to understand the release pattern and the link to the formation of fly ash and aerosols in full-scale waste incinerators. The release of metals, S and Cl from four dedicated waste fractions was quantified as a function of temperature in a lab-scale fixed-bed reactor. The waste fractions comprised chromated copper arsenate (CCA) impregnated wood, shoes, automotive shredder waste and PVC (poly-vinyl-chloride). The waste fractions were characterized by use of wet chemical analysis, and, based on the chemical composition of the initial fuel sample and the ash residue after the experiments; the release of inorganic elements was quantified. The lab-scale release results were then compared with results from a related, full-scale partitioning study, in which test runs with the addition of similar, dedicated waste fractions to a base-load waste had been performed in a grate-fired WtE boiler. In general, the elements Al, Ca, Cr, Cu, Fe, Mg, Si and Ti were not released, in consistency with the non-volatile nature of these elements. The elements Pb, Zn, Cl, S, Na, K and As, on the other hand, were released to a significant extent, and the release pattern was found to be both temperature dependent and fuel specific. Possible release mechanisms were discussed in relation to the chemical characteristics of each fuel, and some of the same release mechanisms as previously suggested for e.g. biomass-based fuels in the literature also seemed to apply for the present waste fractions.     

Cationic peptides that increase the thermal stabilities of 2'-O-MeRNA/RNA duplexes but do not affect DNA/DNA melting

Several different cationic nonapeptides have been synthesized and investigated with respect to how they can influence the thermal melting of 2′‐O‐methylRNA/RNA and DNA/DNA duplexes. Each peptide has a C‐terminal L ‐phenylalanine unit and is otherwise uniformly composed of a sequence of a specific basic D ‐amino acid that in most cases will be largely charged at neutral pH. These N‐terminal octamer stretches are composed variously of the amino acids D ‐lysine, D ‐diaminobutyric acid (D ‐Dab), D ‐diaminopropionic acid (D ‐Dap), or D ‐histidine. None of the peptides substantially affected the thermal melting of DNA/DNA duplexes, which was in sharp contrast with their effects on 2′‐O‐methylRNA/RNA duplexes. In particular, the peptides based on diaminopropionic and diaminobutyric acid units had strong positive effects on the melting temperatures of the 2′‐O‐methylRNA duplexes (up to 16 °C higher with 1 equivalent of peptide) at pH 7, whereas at pH 6 the effect was even more drastic (ΔT_m up to +25 °C). The shorter R groups of the Dap and Dab groups appear to have a better length than lysine for enhancement of the thermal melting of the 2′‐O‐methylRNA/RNA duplex, an effect that is more pronounced at lower pH but substantial even at pH 7, although the Dap derivative is not likely to be fully protonated. The dramatic difference between the influence, or lack thereof, on the 2′‐O‐methylRNA/RNA and the DNA/DNA thermal meltings suggest that, although electrostatic interactions probably play a role, there is another major and structurally dependent component influencing the properties of the duplexes. This is also seen in the observation that the oligo‐Dap and oligo‐Dab peptides give greater melting point enhancements than both the lysine peptide (with a longer side chain) and a β‐linked Dap peptide with a shorter side chain and a longer backbone.     

Structure-activity relationship study of 16 a-thiocamptothecins: an integrated in vitro and in silico approach

The instability of the hydroxylactone E ring represents a critical drawback of camptothecins, because the lactone ring is recognized to be essential for stabilization of topoisomerase I‐mediated DNA cleavage. In an attempt to investigate the effect of the thiopyridone pharmacophofore on the molecular and pharmacological features of the drug, we prepared a series of novel 16 a‐thiocamptothecin analogues. Due to the sulfur atom, a destabilization of the hydrogen bond between the hydroxy group in position 17 of the opened E ring and the carbonyl of the pyridone moiety is predicted, thus shifting the equilibrium toward the closed lactone form and increasing the lipophilic properties of the compounds. This feature was associated with superior antiproliferative potency, with reduced interaction with the human serum albumin and with substantial increase of the persistence of the topoisomerase I–DNA cleavable complex. These effects were prominent for thio‐SN38, the most active compound of the series. The favorable interactions at the molecular and cellular level of the reported thiocamptothecins confer promising features, and these compounds warrant preclinical development.     

Benin 2025—Balancing Future Water Availability and Demand Using the WEAP ‘Water Evaluation and Planning’ System

In Benin, annual water availability per capita far exceeds the critical threshold of about 1,700 m³, but during the dry season, water scarcity occurs at the local scale. By modeling the water balance of the Ouémé–Bonou catchment with WEAP (Water Evaluation and Planning System), this study aimed at analyzing Benin’s future water situation under different scenarios of socio-economic development and climate change until 2025. The results show that the pressure on Benin’s water resources will increase, leading to greater competition for surface water. Furthermore, financial and technological constraints hinder a satisfactory development, and exploration of groundwater and reservoir resources. However, improvements are most needed, especially in rural areas. Decreasing inflows and groundwater recharge due to climate change aggravate this situation. Even though there are uncertainties and constraints concerning the model and input data, this study shows that the WEAP results offer a solid basis to assist planners in developing recommendations for future water resource management by revealing hot spots of action.     

Analysis of PCR-based methods for characterization of Listeria monocytogenes strains isolated from different sources

Listeria monocytogenes strains, isolated from various sources (food, environment, and animals), were used to test different PCR-based methods to investigate their capability to define the strain origin. RAPD-PCR with three primers and the SAU-PCR method, in which the DNA was first digested with the Sau3A restriction endonuclease and then amplified with a primer designed on the restriction site, were carried out, and the profiles obtained were used to perform cluster analysis. Based on the cluster analysis of Listeria spp. strains, obtained from international collections, the coefficient of similarity was selected. The results obtained showed that the methods tested in the study gave different levels of differentiation between the strains tested. The RAPD protocol using the P1254 primer and the SAU-PCR gave appreciable results only for strains isolated from animals and from a food processing plant in two different periods of the year 2003. Better differentiation was observed using the RAPD-PCR with primer D8635. As a matter of fact, it was able to distinguish L. monocytogenes obtained from different species of animals, different food samples and strains from the same production plant isolated in different periods of the year. Also primer M13 gave positive results, but the coefficient of similarity to use had to be increased to 80%. On the basis of the results observed, RAPD-PCR with primers D8635 and M13 should be considered reliable tools for epidemiological investigations focusing on L. monocytogenes.     

Putative mechanisms of kiwifruit on maintenance of normal gastrointestinal function

ABSTRACT

Kiwifruits are recognized as providing relief from constipation and symptoms of constipation-predominant irritable bowel syndrome (IBS-C). However, the underlying mechanisms, specifically in regards to gastrointestinal transit time and motility, are still not completely understood. This review provides an overview on the physiological and pathophysiological processes underlying constipation and IBS-C, the composition of kiwifruit, and recent advances in the research of kiwifruit and abdominal comfort. In addition, gaps in the research are highlighted and scientific studies of other foods with known effects on the gastrointestinal tract are consulted to find likely mechanisms of action. While the effects of kiwifruit fiber are well documented, observed increases in gastrointestinal motility caused by kiwifruit are not fully characterized.

There are a number of identified mechanisms that may be activated by kiwifruit compounds, such as the induction of motility via protease-activated signaling, modulation of microflora, changes in colonic methane status, bile flux, or mediation of inflammatory processes.