Synthesis and Enzymatic Deprotection of Fully Protected 2′‐5′ Oligoadenylates (2‐5A): Towards a Prodrug Strategy for Short 2‐5A

Fully protected pA2′p5′A2′p5′A trimers 1a and 1b have been prepared as prodrug candidates for a short 2′‐5′ oligoadenylate, 2‐5A, and its 3′‐O‐Me analog, respectively. The kinetics of hog liver carboxyesterase (HLE)‐triggered deprotection in HEPES buffer (pH 7.5) at 37° has been studied. The deprotection of 1a turned out to be very slow, and 2‐5A never appeared in a fully deprotected form. By contrast, a considerable proportion of 1b was converted to the desired 2‐5A trimer, although partial removal of the 3′‐O‐[(acetyloxy)methyl] group prior to exposure of the adjacent phosphodiester linkage resulted in 2′,5′→3′,5′ phosphate migration and release of adenosine as side reactions.     

Topical superantigen exposure induces epidermal accumulation of CD8+ T cells, a mixed Th1/Th2-type dermatitis and vigorous production of IgE antibodies in the murine model of atopic dermatitis

Patients with atopic dermatitis (AD) have repeated cutaneous exposure to both environmental allergens and superantigen-producing strains of Staphylococcus aureus. We used a murine model of AD to investigate the role of staphylococcal enterotoxin B (SEB) in the modulation of allergen-induced skin inflammation. Mice were topically exposed to SEB, OVA, a combination of OVA and SEB (OVA/SEB), or PBS. Topical SEB and OVA/SEB exposure induced epidermal accumulation of CD8+ T cells and TCRVbeta8+ cells in contrast to OVA application, which induced a mainly dermal infiltration of CD4+ cells. SEB and OVA/SEB exposure elicited a mixed Th1/Th2-associated cytokine and chemokine expression profile within the skin. Restimulation of lymph node cells from OVA- and OVA/SEB-exposed mice with OVA elicited strong production of IL-13 protein, whereas substantial amounts of IFN-gamma protein were detected after SEB stimulation of cells derived from SEB- or OVA/SEB-exposed mice. Topical SEB treatment elicited vigorous production of SEB-specific IgE and IgG2a Abs and significantly increased the production of OVA-specific IgE and IgG2a Abs. The present study shows that topical exposure to SEB provokes epidermal accumulation of CD8+ T cells, a mixed Th2/Th1 type dermatitis and vigorous production of specific IgE and IgG2a Abs, which can be related to the chronic phase of atopic skin inflammation.     

Phytoplankton community responses to nutrient and iron enrichment under different nitrogen to phosphorus ratios in the northern Baltic Sea

The impact of nutrient enrichment on the phytoplankton community structure, and particularly cyanobacteria, was studied in a 3-week mesocosm experiment conducted in August 2001 in the Archipelago Sea, a part of the northern Baltic Sea. The factorial design experiment included daily additions of nitrogen (N) and phosphorus (P) at two mass ratios, 1N:1P and 7N:1P, respectively, additions of iron (Fe) and a synthetic chelator, ethylenediaminetetraacetic acid (EDTA). The floating enclosures (400 l) were sampled for analyses of phytoplankton biomass and community structure, phytoplankton primary production, chlorophyll a, nutrients, and hepatotoxins. Chlorophyll a concentration, phytoplankton biomass and primary production increased most in the 7N:1P treatment. The increase was mainly due to an abundant growth of chlorophytes (Dictyosphaerium subsolitarium, Kirchneriella spp., Monoraphidium contortum, and Oocystis spp.), pennate diatoms (especially Nitzschia spp.), dinophytes and the chroococcalean cyanobacterium Synechococcus sp. The nutrient enrichments had no effect on the total biomass of N₂-fixing cyanobacteria. Nevertheless, the biomass of Anabaena spp. was highest in the enrichments with a low N/P ratio. Chlorophyll a concentration and total phytoplankton biomass were not affected by Fe or EDTA, but Fe alone had a positive effect on the chlorophyte Kirchneriella sp. The N₂-fixing cyanobacteria Aphanizomenon sp. responded positively to Fe alone and to both Fe and EDTA added together. The hepatotoxin concentration increased during the experiment, but no clear responses to nutrient enrichments were found. Our study showed species-specific responses to nutrient enrichments among the N₂-fixing cyanobacteria. Although the total phytoplankton production was not Fe-limited; the availability of Fe clearly affected the phytoplankton community structure.     

CC chemokine ligand 18, an atopic dermatitis-associated and dendritic cell-derived chemokine, is regulated by staphylococcal products and allergen exposure

Atopic dermatitis is a chronic inflammatory skin disease with a steadily increasing prevalence. Exposure to allergens or bacterial superantigens triggers T and dendritic cell (DC) recruitment and induces atopic skin inflammation. In this study, we report that among all known chemokines CCL18/DC-CK1/PARC represents the most highly expressed ligand in atopic dermatitis. Moreover, CCL18 expression is associated with an atopic dermatitis phenotype when compared with other chronic inflammatory skin diseases. DCs either dispersed within the dermis or clustering at sites showing perivascular infiltrates are abundant sources of CCL18. In vitro, microbial products including LPS, peptidoglycan, and mannan, as well as the T cell-derived activation signal CD40L, induced CCL18 in monocytes. In contrast to monocytes, monocyte-derived, interstitial-type, and Langerhans-type DCs showed a constitutive and abundant expression of CCL18. In comparison to Langerhans cells, interstitial-type DCs produced higher constitutive levels of CCL18. In vivo, topical exposure to the relevant allergen or the superantigen staphylococcal enterotoxin B, resulted in a significant induction of CCL18 in atopic dermatitis patients. Furthermore, in nonatopic NiSO4-sensitized individuals, only relevant allergen but not irritant exposure resulted in the induction of CCL18. Taken together, findings of the present study demonstrate that CCL18 is associated with an atopy/allergy skin phenotype, and is expressed at the interface between the environment and the host by cells constantly screening foreign Ags. Its regulation by allergen exposure and microbial products suggests an important role for CCL18 in the initiation and amplification of atopic skin inflammation.     

Net climate impacts of forest biomass production and utilization in managed boreal forests

In this work, we studied the potentials offered by managed boreal forests and forestry to mitigate the climate change using forest‐based materials and energy in substituting fossil‐based materials (concrete and plastic) and energy (coal and oil). For this purpose, we calculated the net climate impacts (radiative forcing) of forest biomass production and utilization in the managed Finnish boreal forests (60°–70°N) over a 90‐year period based on integrated use forest ecosystem model simulations (on carbon sequestration and biomass production of forests) and life‐cycle assessment (LCA) tool. When studying the effects of management on the radiative forcing in a system integrating the carbon sink/sources dynamics in both biosystem and technosystem, the current forest management (baseline management) was used a reference management. Our results showed that the use of forest‐based materials and energy in substituting fossil‐based materials and energy would provide an effective option for mitigating climate change. The negative climate impacts could be further decreased by maintaining forest stocking higher over the rotation compared to the baseline management and by harvesting stumps and coarse roots in addition to logging residues in the final felling. However, the climate impacts varied substantially over time depending on the prevailing forest structure and biomass assortment (timber, energy biomass) used in substitution.     

CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation

Atopic dermatitis represents a chronically relapsing skin disease with a steadily increasing prevalence of 10-20% in children. Skin-infiltrating T cells, dendritic cells (DC), and mast cells are thought to play a crucial role in its pathogenesis. We report that the expression of the CC chemokine CCL1 (I-309) is significantly and selectively up-regulated in atopic dermatitis in comparison to psoriasis, cutaneous lupus erythematosus, or normal skin. CCL1 serum levels of atopic dermatitis patients are significantly higher than levels in healthy individuals. DC, mast cells, and dermal endothelial cells are abundant sources of CCL1 during atopic skin inflammation and allergen challenge, and Staphylococcus aureus-derived products induce its production. In vitro, binding and cross-linking of IgE on mast cells resulted in a significant up-regulation of this inflammatory chemokine. Its specific receptor, CCR8, is expressed on a small subset of circulating T cells and is abundantly expressed on interstitial DC, Langerhans cells generated in vitro, and their monocytic precursors. Although DC maintain their CCR8+ status during maturation, brief activation of circulating T cells recruits CCR8 from intracytoplamic stores to the cell surface. Moreover, the inflammatory and atopy-associated chemokine CCL1 synergizes with the homeostatic chemokine CXCL12 (SDF-1alpha) resulting in the recruitment of T cell and Langerhans cell-like DC. Taken together, these findings suggest that the axis CCL1-CCR8 links adaptive and innate immune functions that play a role in the initiation and amplification of atopic skin inflammation.     

Introduction of lanthanide(III) chelates to oligopeptides on solid phase

The synthesis of oligopeptide building blocks for the introduction of nonluminescent and luminescent lanthanide(III) chelates to the oligopeptide structure on the solid phase is described. The oligopeptide conjugates synthesized were used in DELFIA-based receptor binding assay (motilin) as well as in LANCE time-resolved fluorescence quenching assay (caspase-3).     

Impacts of nutrient enrichment and sediment on phytoplankton community structure in the northern Baltic Sea

A three-week mesocosm experiment was conducted in order to study the effects of bottom sediment and nutrient enrichment on phytoplankton and zooplankton community structure in the Archipelago Sea, northern Baltic Sea. The transparent polyethylene enclosures included the whole water column and varied in volume from 30 to 40 m³. There were two types of enclosures: some with natural sediment as a bottom and others with a plastic bottom. The experiment was a 2 × 2 factorial design with presence of sediment and nutrient enrichment as treatment factors. Both the sediment presence and nutrient enrichment significantly increased water nutrient concentrations and the rate of primary production. However, external nutrient enrichment and the presence of sediment stimulated the growth of different phytoplankton groups, indicating that the effect of sediment was not related to nutrient fluxes alone, but involved more complex interactions. External nutrient enrichment was primarily channelled to picoplanktonic cyanobacteria, the biomass of which increased four- to fivefold due to enrichment. The presence of sediment increased the biomass of cryptophytes, chrysophytes and prasinophytes, but decreased the biomass of N₂-fixing cyanobacteria. Zooplankton biomass increased during the experiment, but was not affected by the treatments. The study shows that sediment plays a significant role in phytoplankton dynamics, underlining the importance of including sediment in shallow-water mesocosm experiments. Handling editor: J. Padisak     

Immobilization and bone structure in humans

Long-term immobilization is known to result in substantial bone loss. The present review examined the existing evidence for deterioration of bone structure during long-term disuse in humans. Paralysis due to spinal cord injury, long-term exposure to microgravity in space or tightly restricted mobility during bed rest provide reasonable models to assess the influence of immobilization on bone structure. Expectedly, the duration of immobilisation was the major determinant of bone loss, but irrespective of whether the skeletal unloading was due to irrecoverable paralysis, long-term spaceflight or bed rest, the mean pattern of structural deterioration of bone, mainly manifest as substantial cortical thinning and trabecular bone loss, was quite similar. However, skeletal responses to disuse can be highly variable between individuals. Apparently the relative decline in individual’s bone loading in relation to loading prior to immobilization accounts for inter-individual variation.     

Biomass,composition and activity of organism assemblages along a salinity gradient in sea ice subjected to river discharge in the Baltic Sea

A study was undertaken to examine the activity and composition of the seasonal Baltic Sea land-fast sea-ice biota along a salinity gradient in March 2003 in a coastal location in the SW coast of Finland. Using a multi-variable data set, the less well-known algal and protozoan communities, and algal and bacterial production in relation to the physical and chemical environment were investigated. Also, the first coincident measurements of bacterial production and dissolved organic matter (DOM) in a sea-ice system are reported. Communities in sea ice were clearly autotrophy-dominated with algal biomass representing 79% of the total biomass. Protozoa and rotifers made up 18% of biomass in the ice and bacteria only 3%. Highest biomasses were found in mid-transect bottom ice. Water column assemblages were clearly more heterotrophic: 39% algae, 12% bacteria and 49% for rotifers and protozoa. Few significant correlations existed between DOM and bacterial variables, reflecting the complex origin of ice DOM. Dynamics of dissolved organic carbon, nitrogen and phosphorus (DOC, DON and DOP) were also uncoupled. A functional microbial loop is likely to be present in the studied ice. Existence of an under-ice freshwater plume affects the ecosystem functioning: Under-ice water communities are influenced directly by river-water mixing, whereas the ice system seems to be more independent—the interaction mainly taking place through the formation of active bottom communities.