A class of potent antimalarials and their specific accumulation in infected erythrocytes

During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.     

Induction of T helper type 2 immunity by a point mutation in the LAT adaptor

The transmembrane protein LAT (linker for activation of T cells) couples the T cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a mutation of a single LAT tyrosine residue showed impeded T cell development. However, later they accumulated polyclonal helper T (TH) cells that chronically produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation caused tissue eosinophilia and massive maturation of plasma cells secreting to immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes an unanticipated inhibitory function for LAT that is critical for the differentiation and homeostasis of TH cells.     

A glycyl radical site in the crystal structure of a class III ribonucleotide reductase

Ribonucleotide reductases catalyze the reduction of ribonucleotides to deoxyribonucleotides. Three classes have been identified, all using free-radical chemistry but based on different cofactors. Classes I and II have been shown to be evolutionarily related, whereas the origin of anaerobic class III has remained elusive. The structure of a class III enzyme suggests a common origin for the three classes but shows differences in the active site that can be understood on the basis of the radical-initiation system and source of reductive electrons, as well as a unique protein glycyl radical site. A possible evolutionary relationship between early deoxyribonucleotide metabolism and primary anaerobic metabolism is suggested.     

Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit

Neural circuits regulate cytokine production to prevent potentially damaging inflammation. A prototypical vagus nerve circuit, the inflammatory reflex, inhibits tumor necrosis factor-α production in spleen by a mechanism requiring acetylcholine signaling through the α7 nicotinic acetylcholine receptor expressed on cytokine-producing macrophages. Nerve fibers in spleen lack the enzymatic machinery necessary for acetylcholine production; therefore, how does this neural circuit terminate in cholinergic signaling? We identified an acetylcholine-producing, memory phenotype T cell population in mice that is integral to the inflammatory reflex. These acetylcholine-producing T cells are required for inhibition of cytokine production by vagus nerve stimulation. Thus, action potentials originating in the vagus nerve regulate T cells, which in turn produce the neurotransmitter, acetylcholine, required to control innate immune responses.     

Delineating the drivers of waning wildlife habitat: The predominance of cotton farming on the fringe of protected areas in the Mid-Zambezi Valley, Zimbabwe

Zimbabwe’s Mid-Zambezi Valley is of global importance for the emblematic mega-fauna of Africa. Over the past 30 years rapid land use change in this area has substantially reduced wildlife habitat. Tsetse control operations are often blamed for this. In this study, we quantify this change for the Dande Communal Area, Mbire District, of the Mid-Zambezi Valley and analyse the contribution of three major potential drivers: (1) increase in human population; (2) increase in cattle population (and the expansion of associated plough-based agriculture), and; (3) expansion of cotton farming. Although direct effects of land use change on wildlife densities could not be proven, our study suggests that the consequences for elephant and buffalo numbers are negative. All three of the above drivers have contributed to the observed land use change. However, we found farmland to have expanded faster than the human population, and to have followed a similar rate of expansion in cattle sparse, tsetse infested areas as in tsetse free areas where cattle-drawn plough agriculture dominates. This implies the existence of a paramount driver, which we demonstrate to be cotton farming. Contrary to common belief, we argue that tsetse control was not the major trigger behind the dramatic land use change observed, but merely alleviated a constraint to cattle accumulation. We argue that without the presence of a cash crop (cotton), land use change would have been neither as extensive nor as rapid as has been observed. Therefore, conservation agencies should be as concerned by the way people farm as they are by population increase. Conserving biodiversity without jeopardising agricultural production will require the development of innovative technological and institutional options in association with policy and market interventions.     

The influence of water stress and air velocity on growth of Impatiens walleriana and Petunia × hybrid

Impatiens walleriana ‘DeZire’ and Petunia × hybrid ‘Tidal Wave’ were subjected to a combination of water stress and exposure to wind to evaluate the potential application of these treatments as an alternative to chemical growth retardation. Air velocities evaluated were 0.1, 0.2, 0.4, 0.8, 1.5, and 4.5 m s⁻¹ and irrigation treatments were either control or 45% water stress based on irrigation occurring when the weight of the plant (plant, pot and peat) was reduced by 25% (control) or 45% (water stress) of the initial weight. The experiment was repeated twice; once in spring and once in summer.     

Tracking Phytophthora infestans with SSR markers within and between seasons – a field study in Sweden

The dynamics of a late blight epidemic and sexual reproduction in Phytophthora infestans were studied in an experimental field in mid‐Sweden. The field was inoculated with six isolates of P. infestans taken from another potato field where sexual reproduction of the pathogen was suspected. Three weeks after inoculation single‐lesion leaflets were sampled and the resulting isolates characterized using microsatellites (SSRs) and mating type as markers. Among the 151 isolates analysed, the inoculum genotypes constituted more than 80% of the genotypes found, with three other genotypes making up the remainder. The following year, P. infestans obtained from soil samples taken from this field were analysed, and six novel genotypes were identified. Genotypes from the previous summer’s population were not detected. Analysis of the genotypes recovered was consistent with them being recombinants, with the previous summer’s population acting as parents. These findings are consistent with the hypothesis that oospores produced during a summer epidemic in Sweden can overwinter and cause infection the next year.     

Inhibition of cancer cell proliferation in vitro by fruit and berry extracts and correlations with antioxidant levels

The effects of 10 different extracts of fruits and berries on cell proliferation of colon cancer cells HT29 and breast cancer cells MCF-7 were investigated. The fruits and berries used were rosehips, blueberries, black currant, black chokeberries, apple, sea buckthorn, plum, lingonberries, cherries, and raspberries. The extracts decreased the proliferation of both colon cancer cells HT29 and breast cancer cells MCF-7, and the effect was concentration dependent. The inhibition effect for the highest concentration of the extracts varied 2-3-fold among the species, and it was in the ranges of 46-74% (average = 62%) for the HT29 cells and 24-68% (average = 52%) for the MCF-7 cells. There were great differences in the content of the analyzed antioxidants in the extracts. The level of the vitamin C content varied almost 100-fold, and the content of total carotenoids varied almost 150-fold among the species. Also in the composition and content of flavonols, hydroxycinnamic acids, anthocyanins, and phenolics were found great differences among the 10 species. The inhibition of cancer cell proliferation seen in these experiments correlated with levels of some carotenoids and with vitamin C levels, present at levels that can be found in human tissues. The same inhibition of cell proliferation could not be found by ascorbate standard alone. This correlation might indicate a synergistic effect of vitamin C and other substances. In MCF-7 cells, the anthocyanins may contribute to the inhibition of proliferation.     

Liming and reacidification reactions of a forest lake ecosystem,lake Lysevatten,in SW Sweden

Long-term monitoring, 1973 to 1987, of reactions to liming and reacidification of a forest lake ecosystem near the Swedish west coast is reported in this study. Treatment of Lake Lysevatten with a slag product of limestone in 1974 resulted in neutralization and a positive alkalinity. Prolonged dissolution proceeded for about 7 yr whereby 86% dissolved. During 1984–86 Lake Lysevatten approached maximum reacidification with high Al concentrations and an affected biota. Asellus aquaticus L. decreased and dominance within chironomid groups approached preliming conditions. However, the most obvious biological change was the development of the filamentous algal genus Mougeotia and increased growth of Sphagnum. Populations of both plants increased notably when pH declined to about 5. Our study suggests that extensive reacidification (pH < 6.0) of limed lakes should be avoided by successive treatments to prevent development of destabilized lake ecosystems.     

Mercury in the Swedish mor layer — linkages to mercury deposition and sources of emission

The report deals with data from 363 Swedish mor samples. The following parameters are discussed: Hg-, organic and Se-concentrations and Hg-quantity in mor, Hg- and S-deposition from Swedish and continental emissions (point sources and diffuse emissions) and precipitation. The results are focused on mean, geographical variations, statistical correlations and calculations to get first insights and order of magnitude data on the linkages between the Hg-contamination of the Swedish mor layer and the various sources of Hg-emissions. Southern Sweden is significantly influenced by continental Hg-emissions. Several previously unknown domestic discharge sources of Hg have been identified. The total amount of Hg in the Swedish mor layer has been estimated to be about 615 t. East. Germany, United Kingdom, West Germany and Poland seem to have contributed with the largest continental emissions of Hg entering the Swedish mor layers. The countries which early started to build up their industry probably are responsible for greater Hg-contamination than indicated by our figures, and vice versa. If no measures are taken to reduce the emissions, the present contamination will continue. Then, the ‘burden of guilt’ ought to be redistributed so that a higher proportion of the Swedish Hg-contamination would be linked to continental discharges since considerable reductions have already occurred as regards Hg-discharges from large Swedish sources. The problems with elevated Hg-levels in the mor layer and, at the end point, the high concentrations of Hg in lake fish in Sweden, will remain far into the next century.