Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88

The IL-1R/Toll-like receptor (TLR) superfamily of receptors has a key role in innate immunity and inflammation. In this study, we report that streptococcal cell wall (SCW)-induced joint inflammation is predominantly dependent on TLR-2 signaling, since TLR-2-deficient mice were unable to develop either joint swelling or inhibition of cartilage matrix synthesis. Myeloid differentiation factor 88 (MyD88) is a Toll/IL-1R domain containing adaptor molecule known to have a central role in both IL-1R/IL-18R and TLR signaling. Mice deficient for MyD88 did not develop SCW-induced arthritis; both joint swelling and disturbance of cartilage chondrocyte anabolic function was completely abolished. Local levels of proinflammatory cytokines and chemokines in synovial tissue washouts were strongly reduced in MyD88-deficient mice. Histology confirmed the pivotal role of MyD88 in acute joint inflammation. TLR-2-deficient mice still allow influx of inflammatory cells into the joint cavity, although the number of cells was markedly reduced. No influx of inflammatory cells was seen in joints of MyD88-deficient mice. In addition, cartilage matrix proteoglycan loss was completely absent in MyD88 knockout mice. These findings clearly demonstrated that MyD88 is a key component in SCW-induced joint inflammation. Since agonists of the Toll-like pathway are abundantly involved in both septic and rheumatoid arthritis, targeting of MyD88 may be a novel therapy in inflammatory joint diseases.     

Phylogeny of the Lake Tanganyika cichlid species flock and its relationship to the Central and East African haplochromine cichlid fish faunas

Lake Tanganyika, the oldest of the East African Great Lakes, harbors the ecologically, morphologically, and behaviorally most complex of all assemblages of cichlid fishes, consisting of about 200 described species. The evolutionary old age of the cichlid assemblage, its extreme degree of morphological differentiation, the lack of species with intermediate morphologies, and the rapidity of lineage formation have made evolutionary reconstruction difficult. The number and origin of seeding lineages, particularly the possible contribution of riverine haplochromine cichlids to endemic lacustrine lineages, remains unclear. Our phylogenetic analyses, based on mitochondrial DNA sequences of three gene segments of 49 species (25% of all described species, up to 2,400 bp each), yield robust phylogenies that provide new insights into the Lake Tanganyika adaptive radiation as well as into the origin of the Central- and East-African haplochromine faunas. Our data suggest that eight ancient African lineages may have seeded the Tanganyikan cichlid radiation. One of these seeding lineages, probably comprising substrate spawning Lamprologus-like species, diversified into six lineages that evolved mouthbrooding during the initial stage of the radiation. All analyzed haplochromines from surrounding rivers and lakes seem to have evolved within the radiating Tanganyikan lineages. Thus, our findings contradict the current hypothesis that ancestral riverine haplochromines colonized Lake Tanganyika to give rise to at least part of its spectacular endemic cichlid species assemblage. Instead, the early phases of the Tanganyikan radiation affected Central and East African rivers and lakes. The haplochromines may have evolved in the Tanganyikan basin before the lake became a hydrologically and ecologically closed system and then secondarily colonized surrounding rivers. Apparently, therefore, the current diversity of Central and East African haplochromines represents a relatively young and polyphyletic fauna that evolved from or in parallel to lineages now endemic to Lake Tanganyika.     

The archaeal respiratory supercomplex SoxM from S. acidocaldarius combines features of quinole and cytochrome c oxidases

The hyperthermoacidophilic archaeon Sulfolobus acidocaldarius has a unique respiratory system with at least two terminal oxidases. Genetic and preliminary biochemical studies suggested the existence of a unique respiratory supercomplex, SoxM. Here we show (i) that all respective genes are translated into polypeptides, and (ii) that the supercomplex can be separated from the alternative oxidase SoxABCD and in that way characterized in a catalytically competent form for the first time. It acts as a quinol oxidase and contains a total of seven metal redox centers. One of it--the blue copper protein sulfocyanin--functionally links two subcomplexes. One is a bb3-type terminal oxidase moiety containing CuA and CuB, whereas the other consists of a Rieske FeS-protein and a homolog to cytochrome b--in this case hosting two hemes As. Based on a 1:1 stoichiometry, 1 mol complex contains 6 mol Fe and 4 mol Cu. Its activity is completely inhibited by cyanide and strongly by aurachin-C and -D derivatives as inhibitors of the quinol binding site. These data suggest that the complex provides two proton pumping sites. Interestingly, subunit-II reveals an unusual pH dependence and is proposed to act as a pH sensor as well as a regulator of catalytic activity via a reversible transition between two states of the CuA ligation. This is a novel hint at how S. acidocaldarius can adapt to and survive in its extreme natural environment.     

The relation between vegetation and soil chemistry gradients in a ground water discharge fen

Abstract. The soil chemistry of a headwater valley fen is influenced by local ground water discharge that supplies base cations and alkalinity to the fen. An irrigation canal just upward of the fen is the source of this alkalinity. The ecological consequences of this artificial system are studied both on the soil and vegetation level. Rich-fen species of the alliance Caricion davallianae are connected to soil water alkalinity and soil base status. They depend directly on the alkaline ground water discharge. In addition, the local input of this water causes a gradient-rich pattern from poor to rich fen, and it is therefore concluded that it is responsible for the presence of intermediate fen vegetation too. High nutrient levels in the irrigation water have not influenced the fen until now. This case study illustrates the possibility for rich fen restoration after acidification. Irrigation with alkaline water is efficient if excess nutrients can be removed.     

Multimodal biomarker discovery for active Onchocerca volvulus infection

The neglected tropical disease onchocerciasis, or river blindness, is caused by infection with the filarial nematode Onchocerca volvulus. Current estimates indicate that 17 million people are infected worldwide, the majority of them living in Africa. Today there are no non-invasive tests available that can detect ongoing infection, and that can be used for effective monitoring of elimination programs. In addition, to enable pharmacodynamic studies with novel macrofilaricide drug candidates, surrogate endpoints and efficacy biomarkers are needed but are non-existent. We describe the use of a multimodal untargeted mass spectrometry-based approach (metabolomics and lipidomics) to identify onchocerciasis-associated metabolites in urine and plasma, and of specific lipid features in plasma of infected individuals (O. volvulus infected cases: 68 individuals with palpable nodules; lymphatic filariasis cases: 8 individuals; non-endemic controls: 20 individuals). This work resulted in the identification of elevated concentrations of the plasma metabolites inosine and hypoxanthine as biomarkers for filarial infection, and of the urine metabolite cis-cinnamoylglycine (CCG) as biomarker for O. volvulus. During the targeted validation study, metabolite-specific cutoffs were determined (inosine: 34.2 ng/ml; hypoxanthine: 1380 ng/ml; CCG: 29.7 ng/ml) and sensitivity and specificity profiles were established. Subsequent evaluation of these biomarkers in a non-endemic population from a different geographical region invalidated the urine metabolite CCG as biomarker for O. volvulus. The plasma metabolites inosine and hypoxanthine were confirmed as biomarkers for filarial infection. With the availability of targeted LC-MS procedures, the full potential of these 2 biomarkers in macrofilaricide clinical trials, MDA efficacy surveys, and epidemiological transmission studies can be investigated.     

Plant functional trait response to environmental drivers across European temperate forest understorey communities

• Functional traits respond to environmental drivers, hence evaluating trait‐environment relationships across spatial environmental gradients can help to understand how multiple drivers influence plant communities. Global‐change drivers such as changes in atmospheric nitrogen deposition occur worldwide, but affect community trait distributions at the local scale, where resources (e.g. light availability) and conditions (e.g. soil pH) also influence plant communities.
• We investigate how multiple environmental drivers affect community trait responses related to resource acquisition (plant height, specific leaf area (SLA), woodiness, and mycorrhizal status) and regeneration (seed mass, lateral spread) of European temperate deciduous forest understoreys. We sampled understorey communities and derived trait responses across spatial gradients of global‐change drivers (temperature, precipitation, nitrogen deposition, and past land use), while integrating in‐situ plot measurements on resources and conditions (soil type, Olsen phosphorus (P), Ellenberg soil moisture, light, litter mass, and litter quality).
• Among the global‐change drivers, mean annual temperature strongly influenced traits related to resource acquisition. Higher temperatures were associated with taller understoreys producing leaves with lower SLA, and a higher proportional cover of woody and obligate mycorrhizal (OM) species. Communities in plots with higher Ellenberg soil moisture content had smaller seeds and lower proportional cover of woody and OM species. Finally, plots with thicker litter layers hosted taller understoreys with larger seeds and a higher proportional cover of OM species.
• Our findings suggest potential community shifts in temperate forest understoreys with global warming, and highlight the importance of local resources and conditions as well as global‐change drivers for community trait variation.

     

Characterization of ISRgn1, a Novel Insertion Sequence of the IS3 Family Isolated from a Bacteriocin-Negative Mutant of Ruminococcus gnavus E1

ISRgn1, an insertion sequence of the IS3 family, has been identified in the genome of a bacteriocin-negative mutant of Ruminococcus gnavus E1. The copy number of ISRgn1 in R. gnavus E1, as well as its distribution among phylogenetically E1-related strains, has been determined. Results obtained suggest that ISRgn1 is not indigenous to the R. gnavus phylogenetic group but that it can transpose in this bacterium.     

Helminth parasites of the Eurasian otter Lutra lutra in southwest Europe

The helminth fauna in 109 Eurasian otters (Lutra lutra L.) from France, Portugal and Spain was analysed, together with 56 faecal samples collected in Portugal and 23 fresh stools from otters included in a reintroduction programme. Seven helminth species were found in L. lutra in southwest Europe: Phagicola sp. (Trematoda), Aonchotheca putorii, Eucoleus schvalovoj, Strongyloides lutrae, Anisakis (third stage larvae) and Dirofilaria immitis (Nematoda), and Gigantorhynchus sp. (Acanthocephala). Eucoleus schvalovoj was the dominant species throughout southwest Europe. Strongyloides lutrae was significantly more prevalent in the Iberian Peninsula than in France. Apart from these two dominant nematodes and A. putorii, the other helminth species were incidental parasites of L. lutra in southwest Europe. The helminth fauna of L. lutra in southwest Europe is, in general, poorer than that reported in eastern Europe and in all other aquatic mustelids in southwest Europe. Phagicola specimens are reported for the first time in a non-marine wild carnivore in Europe. The prevalences of E. schvalovoj and S. lutrae obtained by necropsy were higher than those observed by coprological analysis using a formalin-ether concentration method (Ritchie). Nevertheless, the culture of fresh faeces appears to be the best method to study infection of L. lutra by Strongyloides.