A Genetic Variation of Lipopolysaccharide Binding Protein Affects the Inflammatory Response and Is Associated with Improved Outcome during Sepsis

LPS binding protein (LBP) is an important innate sensor of microbial cell wall structures. Frequent functionally relevant mutations exist and have been linked to influence susceptibility to and course of bacterial infections. We examined functional properties of a single nucleotide polymorphism resulting in an exchange of phenylalanine to leucine at position 436 of LBP (rs2232618) and compared the frequent variant of the molecule with the rare one in ligand binding experiments. We then stimulated RAW cells with bacterial ligands in the presence of serum obtained from individuals with different LBP genotypes. We, furthermore, determined the potential effects of structural changes in the molecule by in silico modeling. Finally, we analyzed 363 surgical patients for this genetic variant and examined incidence and course of sepsis following surgery. We found that binding of LBP to bacterial ligands was reduced, and stimulation of RAW cells resulted in an increased release of TNF when adding serum from individuals carrying the F436L variant as compared with normal LBP. In silico analysis revealed structural changes of LBP, potentially explaining some of the effects observed for the LBP variant. Finally, patients carrying the F436L variant were found to be similarly susceptible for sepsis. However, we observed a more favorable course of severe infections in this cohort. Our findings reveal new insights into LPS recognition and the subsequent activation of the innate immune system brought about by LBP. The identification of a genetic variant of LBP influencing the course of sepsis may help to stratify individuals at risk and thus reduce clinical complications of patients.Peer Reviewe

Influence of Forest Management Regimes on Forest Dynamics in the Upstream Region of the Hun River in Northeastern China

Balancing forest harvesting and restoration is critical for forest ecosystem management. In this study, we used LANDIS, a spatially explicit forest landscape model, to evaluate the effects of 21 alternative forest management initiatives which were drafted for forests in the upstream region of the Hun River in northeastern China. These management initiatives included a wide range of planting and harvest intensities for Pinus koraiensis, the historically dominant tree species in the region. Multivariate analysis of variance, Shannon's Diversity Index, and planting efficiency (which indicates how many cells of the target species at the final year benefit from per-cell of the planting trees) estimates were used as indicators to analyze the effects of planting and harvesting regimes on forests in the region. The results showed that the following: (1) Increased planting intensity, although augmenting the coverage of P. koraiensis, was accompanied by decreases in planting efficiency and forest diversity. (2) While selective harvesting could increase forest diversity, the abrupt increase of early succession species accompanying this method merits attention. (3) Stimulating rapid forest succession may not be a good management strategy, since the climax species would crowd out other species which are likely more adapted to future climatic conditions in the long run. In light of the above, we suggest a combination of 30% planting intensity with selective harvesting of 50% and 70% of primary and secondary timber species, respectively, as the most effective management regime in this area. In the long run this would accelerate the ultimate dominance of P. koraiensis in the forest via a more effective rate of planting, while maintaining a higher degree of forest diversity. These results are particularly useful for forest managers constrained by limited financial and labor resources who must deal with conflicts between forest harvesting and restoration

Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient\u27s PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and TNF-α production, which enhanced fungal killing in an interdependent manner. Deficiency of either Dectin-1 or CARD9 was associated with more severe fungal disease, recapitulating the human observation. Because these data implicated impaired Dectin-1 responses in susceptibility to phaeohyphomycosis, we evaluated 17 additional unrelated patients with severe forms of the infection. We found that 12 out of 17 carried deleterious CLEC7A mutations associated with an altered Dectin-1 extracellular C-terminal domain and impaired Dectin-1-dependent cytokine production. Thus, we show that Dectin-1 and CARD9 promote protective TNF-α- and IL-1β-mediated macrophage defense against C. cassiicola. More broadly, we demonstrate that human Dectin-1 deficiency may contribute to susceptibility to severe phaeohyphomycosis by certain dematiaceous fungi

Is Douglas Fir [Pseudotsuga menziesii (Mirbel) Franco] Invasive in Central Europe? A Case Study From South-West Germany

Worldwide, forestry must face several challenges during the UN Decade on Ecosystem Restoration. The decline of biodiversity and ecosystem services, ongoing deforestation, climate change, and biological invasions must be mitigated with forest restoration and by applying sustainable forest management. Experiences with the integration of non-native tree species into forest management in many parts of the world show benefits but also trade-offs regarding sustainability. In Central Europe, Douglas fir [ Pseudotsuga menziesii (Mirbel) Franco], originating from Northern America, has been introduced by forestry and managed for more than one and a half centuries. Growth characteristics, drought tolerance, and timber quality are major reasons which make this tree species attractive for forestry and wood industry. Whether Douglas fir might be invasive with potential trade-offs regarding biodiversity, uncontrolled regeneration, and spread is not yet fully understood and controversially debated. We investigated the regeneration of Douglas fir in the Spessart mountains, a vast woodland in south-western Germany which has a considerable cover of anthropogenic coniferous afforestations. We sampled the regeneration of Douglas fir by differentiating height growth classes in various forest-stand types, taking the distance from mature mother trees, abiotic site conditions (e.g., water balance and soil properties), light supply, forest-stand characteristics, ground vegetation, and browsing pressure into account. Also integrating the individual regeneration of the accompanying tree species, we applied multivariate analyses. Most of our investigated variables did not show a significant correlation with Douglas fir regeneration. However, results point to a positive relationship of spontaneous Douglas fir regeneration at moist and light sites as well as in close distance to potential seed trees. The analysis of the current invasion potential did not reveal a major risk under the given site conditions in the study area.Bayerisches Staatsministerium für Ernährung, Landwirtschaft und Forste

Vegetation Succession on Degraded Sites in the Pomacochas Basin (Amazonas, N Peru)—Ecological Options for Forest Restoration

The Andes of northern Peru are still widely covered with forests, but increasingly suffer from habitat fragmentation. Subsequent soil degradation often leads to the abandonment of overused forests and pastures. Ecological knowledge on the restoration potential, e.g., on dependencies of soil conditions and altitude, is scarce. Therefore, we compared soil and vegetation patterns along nine transects within the upper Pomacochas Basin, which is an important biodiversity corridor along the Andes, between remaining forests, succession sites and pastures. Anthropogenic successional and disturbance levels, geological substrate, and altitude have the most important ecological impacts on vegetation and tree species composition. Species responded to sandstone versus calcareous substrates, but also to depths of the organic soil layer, and light conditions. The absence of organic layers under pastures contrasted with the accumulation of thick organic layers under forest cover. Vegetation composition at succession sites revealed certain starting points (herbal stage, bush stage, or secondary forest) for restoration that will determine the length of regeneration paths. Pre-forest patches of Alchornea sp. and Parathesis sp. may act as habitat stepping stones for expeditiously restoring biocorridors for wildlife. The key findings can contribute to the sustainable use and conservation of biodiversity in a fragile ecoregion

A de novo frameshift mutation in ZEB2 causes polledness, abnormal skull shape, small body stature and subfertility in Fleckvieh cattle

International audiencePolledness in cattle is an autosomal dominant trait. Previous studies have revealed allelic heterogeneity at the polled locus and four different variants were identified, all in intergenic regions. In this study, we report a case of polled bull (FV-Polled1) born to horned parents, indicating a de novo origin of this polled condition. Using 50K genotyping and whole genome sequencing data, we identified on chromosome 2 an 11-bp deletion (AC_000159.1:g.52364063_52364073del; Del11) in the second exon of ZEB2 gene as the causal mutation for this de novo polled condition. We predicted that the deletion would shorten the protein product of ZEB2 by almost 91%. Moreover, we showed that all animals carrying Del11 mutation displayed symptoms similar to Mowat-Wilson syndrome (MWS) in humans, which is also associated with genetic variations in ZEB2. The symptoms in cattle include delayed maturity, small body stature and abnormal shape of skull. This is the first report of a de novo dominant mutation affecting only ZEB2 and associated with a genetic absence of horns. Therefore our results demonstrate undoubtedly that ZEB2 plays an important role in the process of horn ontogenesis as well as in the regulation of overall development and growth of animals