Elevated anti-malarial IgE in asymptomatic individuals is associated with reduced risk for subsequent clinical malaria

Immunological characteristics were assessed for prospective risk of clinical malaria in a longitudinally followed population in a holoendemic area of Tanzania. Baseline characteristics including crude Plasmodium falciparum extract-specific IgE and IgG; total IgE; and parasitological indices, e.g. number of P. falciparum clones, were investigated among 700 asymptomatic individuals. Cox regression analysis estimated the risk of succumbing to a new clinical episode during a 40 weeks follow up. High anti-P. falciparum IgE levels were associated with reduced risk of acute malaria in all age groups independently of total IgE levels. Statistically significant reduced odds ratio of 0.26 (95% CI, 0.09-0.72, P=0.010) and 0.44 (95% CI, 0.19-0.99, P=0.047) for the two highest fifths, respectively was observed after adjustment for age, sex, total IgE, numbers of parasite clones per infection and HIV-1 seropositivity. In contrast, high levels of malaria specific IgG or total IgE were not associated with reduced risk to succumb to a new clinical episode. A protective effect of asymptomatic multiclonal P. falciparum infections was also confirmed. For the first time, anti-malarial IgE levels in asymptomatic individuals in endemic area are found to be associated with reduced risk for subsequent malaria disease. Specific IgE antibodies may play role in maintaining anti-malarial immunity, or indicate other aspects of immune function relevant for protection against malaria.     

Involvement of Smad signaling in sphingosine 1-phosphate-mediated biological responses of keratinocytes

The lysophospholipid sphingosine 1-phosphate and the cytokine-transforming growth factor beta are both released from degranulating platelets at wound sites, suggesting a broad spectrum of effects involved in wound healing. Interestingly, both of these molecules have been previously shown to induce chemotaxis but to strongly inhibit the growth of keratinocytes, while stimulating the proliferation of fibroblasts. In contrast to sphingosine 1-phosphate, the signaling cascade of the growth factor has been extensively examined. Specifically, Smad3 has been shown to be an essential mediator of transforming growth factor beta-dependent chemotaxis of keratinocytes and mediates, in part, its growth-inhibitory effect. Here we show that sphingosine 1-phosphate, independently of transforming growth factor beta secretion, induces a rapid phosphorylation of Smad3 on its C-terminal serine motif and induces its partnering with Smad4 and the translocation of the complex into the nucleus. Moreover, sphingosine 1-phosphate fails to induce chemotaxis or inhibit the growth of Smad3-deficient keratinocytes, suggesting that Smad3 plays an unexpected functional role as a new target in sphingosine 1-phosphate signaling. Both sphingosine 1-phosphate receptors and the transforming growth factor beta-type I receptor serine/threonine kinase are essential for activation of Smad3 by this lysophospholipid and the dependent biological responses, indicating a novel cross-talk between serine/threonine kinase receptors and G-protein coupled receptors.     

Fermentation performance of engineered and evolved xylose-fermenting Saccharomyces cerevisiae strains

Lignocellulose hydrolysate is an abundant substrate for bioethanol production. The ideal microorganism for such a fermentation process should combine rapid and efficient conversion of the available carbon sources to ethanol with high tolerance to ethanol and to inhibitory components in the hydrolysate. A particular biological problem are the pentoses, which are not naturally metabolized by the main industrial ethanol producer Saccharomyces cerevisiae. Several recombinant, mutated, and evolved xylose fermenting S. cerevisiae strains have been developed recently. We compare here the fermentation performance and robustness of eight recombinant strains and two evolved populations on glucose/xylose mixtures in defined and lignocellulose hydrolysate-containing medium. Generally, the polyploid industrial strains depleted xylose faster and were more resistant to the hydrolysate than the laboratory strains. The industrial strains accumulated, however, up to 30% more xylitol and therefore produced less ethanol than the haploid strains. The three most attractive strains were the mutated and selected, extremely rapid xylose consumer TMB3400, the evolved C5 strain with the highest achieved ethanol titer, and the engineered industrial F12 strain with by far the highest robustness to the lignocellulosic hydrolysate.     

Effect of channel block on the spiking activity of excitable membranes in a stochastic Hodgkin-Huxley model

The influence of intrinsic channel noise on the spontaneous spiking activity of poisoned excitable membrane patches is studied by use of a stochastic generalization of the Hodgkin-Huxley model. Internal noise stemming from the stochastic dynamics of individual ion channels is known to affect the collective properties of the whole ion channel cluster. For example, there exists an optimal size of the membrane patch for which the internal noise alone causes a regular spontaneous generation of action potentials. In addition to varying the size of ion channel clusters, living organisms may adapt the densities of ion channels in order to optimally regulate the spontaneous spiking activity. The influence of a channel block on the excitability of a membrane patch of a certain size is twofold: first, a variation of ion channel densities primarily yields a change of the conductance level; second, a down-regulation of working ion channels always increases the channel noise. While the former effect dominates in the case of sodium channel block resulting in a reduced spiking activity, the latter enhances the generation of spontaneous action potentials in the case of a tailored potassium channel blocking. Moreover, by blocking some portion of either potassium or sodium ion channels, it is possible to either increase or decrease the regularity of the spike train.     

Neuroprotective effects and intracellular signaling pathways of erythropoietin in a rat model of multiple sclerosis

In multiple sclerosis (MS), long-term disability is primarily caused by axonal and neuronal damage. We demonstrated in a previous study that neuronal apoptosis occurs early during experimental autoimmune encephalomyelitis, a common animal model of MS. In the present study, we show that, in rats suffering from myelin oligodendrocyte glycoprotein (MOG)-induced optic neuritis, systemic application of erythropoietin (Epo) significantly increased survival and function of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve. We identified three independent intracellular signaling pathways involved in Epo-induced neuroprotection in vivo: Protein levels of phospho-Akt, phospho-MAPK 1 and 2, and Bcl-2 were increased under Epo application. Using a combined treatment of Epo together with a selective inhibitor of phosphatidylinositol 3-kinase (PI3-K) prevented upregulation of phospho-Akt and consecutive RGC rescue. We conclude that in MOG-EAE the PI3-K/Akt pathway has an important influence on RGC survival under systemic treatment with Epo.     

New separation-free assay technique for SNPs using two-photon excitation fluorometry

A new separation-free method for detection of single nucleotide polymorphisms (SNPs) is described. The method is based on the single base extension principle, fluorescently labeled dideoxy nucleotides and two-photon fluorescence excitation technology, known as ArcDia™ TPX technology. In this assay technique, template-directed single base extension is carried out for primers which have been immobilized on polymer microparticles. Depending on the sequence of the template DNA, the primers are extended either with a labeled or with a non-labeled nucleotide. The genotype of the sample is determined on the basis of two-photon excited fluorescence of individual microparticles. The effect of various assay condition parameters on the performance of the assay method is studied. The performance of the new assay method is demonstrated by genotyping the SNPs of human individuals using double-stranded PCR amplicons as samples. The results show that the new SNP assay method provides sensitivity and reliability comparable to the state-of-the-art SNaPshot™ assay method. Applicability of the new method in routine laboratory use is discussed with respect to alternative assay techniques.     

Calystegines in Calystegia sepium do not inhibit fungal growth and invertase activity but interact with plant invertase

Abstract: Calystegines are alkaloidal glycosidase inhibitors. They accumulate predominantly in young and meristemic parts of Calystegia sepium (Convolvulaceae). C. sepium, bindweed, infests meadows and cereal fields and is difficult to control chemically. Fungal pathogens against C. sepium are established as mycoherbicides. Stagonospora convolvuli LA39 attacks C. sepium and does not affect crop plants, but young plants of C. sepium are less susceptible to the fungus. The interaction of Stagonospora convolvuli with calystegines was investigated. Further, endophytic fungi of several classes were isolated from wild-grown Calystegia sepium leaves, and selected strains were tested for interaction with calystegines. Fungal growth on agar containing calystegines was not affected considerably. Plants in climate chambers were infected with an endophyte, Phomopsis, and with the fungal pathogen, Stagonospora convolvuli. Calystegine levels were measured in infected and non-infected plant tissues. Accumulation depended on developmental stage of the plant tissue and was not influenced by infection. Acid invertase was measured from fungal mycelia and from infected and non-infected plant tissues. Fungal acid invertase activity was not inhibited by 10 mM calystegine B₂, while invertase from C. sepium leaves was inhibited. It is concluded that calystegines do not inhibit fungal development and sucrose consumption under the conditions of the present investigation, but may act by redirection of plant carbohydrate metabolism.     

Thermophilic methanogenic Archaea in compost material: occurrence, persistence and possible mechanisms for their distribution to other environments

Since compost is widely used as soil amendment and the fact that during the processing of compost material high amounts of microorganisms are released into the air, we investigated whether compost may act as a carrier for thermophilic methanogens to temperate soils.

All eight investigated compost materials showed a clear methane production potential between 0.01 and 0.98 μmol CH₄ g dw⁻¹ h⁻¹ at 50 °C. Single strand conformation polymorphism (SSCP) and cloning analysis indicated the presence of Methanosarcina thermophila, Methanoculleus thermophilus, and Methanobacterium formicicum.

Bioaerosols collected during the turning of a compost pile showed both a highly similar SSCP profile compared to the corresponding compost material and clear methane production during anoxic incubation in selective medium at 50 °C. Both observations indicated a considerable release of thermophilic methanogens into the air.

To analyse the persistence of compost-borne thermophilic methanogens in temperate oxic soils, we therefore studied their potential activity in compost and compost/soil mixtures, which was brought to a meadow soil, as well as in an agricultural soil fertilised with compost. After 24 h anoxic incubation at 50 °C, all samples containing compost showed a clear methanogenic activity, even 1 year after application.

In combination with the in vitro observed resilience of the compost-borne methanogens against desiccation and UV radiation we assume that compost material acts as an effective carrier for the distribution of thermophilic methanogens by fertilisation and wind.     

Seasonal Viral Loop Dynamics in Two Large Ultraoligotrophic Antarctic Freshwater Lakes

The effect of viruses on the microbial loop, with particular emphasis on bacteria, was investigated over an annual cycle in 2003–2004 in Lake Druzhby and Crooked Lake, two large ultraoligotrophic freshwater lakes in the Vestfold Hills, Eastern Antarctica. Viral abundance ranged from 0.16 to 1.56 × 10⁹ particles L^-1;1 and bacterial abundances ranged from 0.10 to 0.24 × 10⁹ cells L^-1;1, with the lowest bacterial abundances noted in the winter months. Virus-to-bacteria ratios (VBR) were consistently low in both lakes throughout the season, ranging from 1.2 to 8.4. lysogenic bacteria, determined by induction with mitomycin C, were detected on three sampling occasions out of 10 in both lakes. In Lake Druzhby and Crooked Lake, lysogenic bacteria made up between 18% and 73% of the total bacteria population during the lysogenic events. Bacterial production ranged from 8.2 to 304.9 × 10⁶ cells L^-1;1 day^-1;1 and lytic viral production ranged from 47.5 to 718.4 × 10⁶ viruslike particles L^-1;1 day^-1;1. When only considering primary production, heterotrophic nanoflagellate (HNF) grazing and viral lysis as the major contributors to the DOC pool (i.e., autochthonous sources), we estimated a high contribution from viruses during the winter months when >60% of the carbon supplied to the DOC pool originated from viral lysis. In contrast, during the summer <20% originated from viral lysis. Our study shows that viral process in ultraoligotrophic Antarctic lakes may be of quantitative significance with respect to carbon flow especially during the dark winter period.     

Natural phenological variation in aspen (Populus tremula): the SwAsp collection

The genus Populus is currently the main model system for genetic, genomic, and physiological research in trees. Phenotypic variation in aspen (Populus tremula) populations growing in different environments across Sweden is expected to reflect genetic variation that is important for local adaptation. To analyze such natural phenotypic and genetic variation, the Swedish Aspen (SwAsp) Collection was established. Trees were taken from 12 different populations across Sweden, from 56° to 66° latitude north and planted in two common gardens in Ekebo (55.9°N) and Sävar (63.4°N). Data related to phenological and growth traits were collected during the second year of growth. Some traits like the date of bud set and leaf area duration showed strong clinal variation patterns with latitude in both field trials, but the date of bud flush did not change along a latitudinal cline. The phenological traits showed moderate within-populations heritabilities, although growth traits showed weaker clinal patterns and lower heritabilities than the phenological traits. This research forms the starting point for the development of the SwAsp collection, a resource facilitating analysis of the natural genetic variation in aspen, the elucidation of the structure and dynamics of aspen populations, and the future identification of the genes controlling adaptive traits using association mapping of selected candidate genes.