Source Community and Assembly Processes Affect the Efficiency of Microbial Microcystin Degradation on Drinking Water Filtration Membranes

Microbial biofilms in gravity-driven membrane (GDM) filtration systems can efficiently degrade the cyanotoxin microcystin (MC), but it is unclear if this function depends on the presence of MC-producing cyanobacteria in the source water habitat. We assessed the removal of MC from added Microcystis aeruginosa biomass in GDMs fed with water from a lake with regular blooms of toxic cyanobacteria (ExpL) or from a stream without such background (ExpS). While initial MC removal was exclusively due to abiotic processes, significantly higher biological MC removal was observed in ExpL. By contrast, there was no difference in MC degradation capacity between lake and stream bacteria in separately conducted liquid enrichments on pure MC. Co-occurrence network analysis revealed a pronounced modularity of the biofilm communities, with a clear hierarchic distinction according to feed water origin and treatment type. Genotypes in the network modules associated with ExpS had significantly more links to each other, indicating that these biofilms had assembled from a more coherent source community. In turn, signals for stochastic community assembly were stronger in ExpL biofilms. We propose that the less “tightly knit” ExpL biofilm assemblages allowed for the better establishment of facultatively MC degrading bacteria, and thus for higher overall functional efficiency

Alfred Lorenzer and the depth-hermeneutic method

This extended article aims to introduce an Anglophone audience to the work of Alfred Lorenzer. As such, it has three main components: it outlines some of Lorenzer's central concepts (the scenic, interaction forms, engrams, symbolisation and desymoblisation, language games and scenic understanding); explores the dialectical relations through which, for Lorenzer, unconscious, bodily and social processes are mutually constituted; and sketches some of the principles informing the depth-hermeneutic method, the tradition of social, cultural and social psychological research to which his ideas gave rise. Throughout, Lorenzer is viewed as seeking to put psychoanalysis on a materialist footing and concerned to assert its critical potential

Multi-objective Optimization of Wind Farm Layouts Under Energy Generation and Noise propagation

Wind farm design deals with the optimal placement of turbines in a wind farm. Past studies have focused on energymaximization, cost-minimization or revenue-maximization objectives. As land is more extensively exploited for onshore wind farms, wind farms are more likely to be in close proximity with human dwellings. Therefore governments, developers, and landowners have to be aware of wind farms’ environmental impacts. After considering land constraints due to environmental features, noise generation remains the main environmental/health concern for wind farm design. Therefore, noise generation is sometimes included in optimization models as a constraint. Here we present continuous-location models for layout optimization that take noise and energy as objective functions, in order to fully characterize the design and performance spaces of the optimal wind farm layout problem. Based on Jensen’s wake model and ISO-9613-2 noise calculations, we used single- and multiobjective genetic algorithms (NSGA-II) to solve the optimization problem. Preliminary results from the biobjective optimization model illustrate the trade-off between energy generation and noise production by identifying several key parts of Pareto frontiers. In addition, comparison of single-objective noise and energy optimization models show that the turbine layouts and the inter-turbine distance distributions are different when considering these objectives individually. The relevance of these results for wind farm layout designers is explored

Unique and conserved functions of B cell-activating factor of the TNF family (BAFF) in the chicken

The chicken represents the best-characterized animal model for B cell development in the so-called gut-associated lymphoid tissue (GALT) and the molecular processes leading to B cell receptor diversification in this species are well investigated. However, the mechanisms regulating B cell development and homeostasis in GALT species are largely unknown. Here we investigate the role played by the avian homologue of B cell-activating factor of the tumor necrosis factor family (BAFF). Flow cytometric analysis showed that the receptor for chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is primarily produced by B cells both in peripheral lymphoid organs and in the bursa of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo studies revealed that chBAFF is required for mature B cell survival. In addition, in vivo neutralization with a decoy receptor led to a reduction of the size and number of B cell follicles in the bursa, demonstrating that, in contrast to humans and mice, in chickens BAFF is also required for the development of immature B cells. Collectively, we show that chBAFF has phylogenetically conserved functions in mature B cell homeostasis but displays unique and thus far unknown properties in the regulation of B cell development in bird

A Novel Modular Antigen Delivery System for Immuno Targeting of Human 6-sulfo LacNAc-Positive Blood Dendritic Cells (SlanDCs)

Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767-777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines

Suitability of external controls for drug evaluation in Duchenne muscular dystrophy

OBJECTIVE: To evaluate the suitability of real-world data (RWD) and natural history data (NHD) for use as external controls in drug evaluations for ambulatory Duchenne muscular dystrophy (DMD). METHODS: The consistency of changes in the 6-minute walk distance (Δ6MWD) was assessed across multiple clinical trial placebo arms and sources of NHD/RWD. Six placebo arms reporting 48-week Δ6MWD were identified via literature review and represented 4 sets of inclusion/exclusion criteria (n = 383 patients in total). Five sources of RWD/NHD were contributed by Universitaire Ziekenhuizen Leuven, DMD Italian Group, The Cooperative International Neuromuscular Research Group, ImagingDMD, and the PRO-DMD-01 study (n = 430 patients, in total). Mean Δ6MWD was compared between each placebo arm and RWD/NHD source after subjecting the latter to the inclusion/exclusion criteria of the trial for baseline age, ambulatory function, and steroid use. Baseline covariate adjustment was investigated in a subset of patients with available data. RESULTS: Analyses included ∼1,200 patient-years of follow-up. Differences in mean Δ6MWD between trial placebo arms and RWD/NHD cohorts ranged from -19.4 m (i.e., better outcomes in RWD/NHD) to 19.5 m (i.e., worse outcomes in RWD/NHD) and were not statistically significant before or after covariate adjustment. CONCLUSIONS: We found that Δ6MWD was consistent between placebo arms and RWD/NHD subjected to equivalent inclusion/exclusion criteria. No evidence for systematic bias was detected. These findings are encouraging for the use of RWD/NHD to augment, or possibly replace, placebo controls in DMD trials. Multi-institution collaboration through the Collaborative Trajectory Analysis Project rendered this study feasible

Neuromatch Academy: a 3-week, online summer school in computational neuroscience

Neuromatch Academy (https://academy.neuromatch.io; (van Viegen et al., 2021)) was designed as an online summer school to cover the basics of computational neuroscience in three weeks. The materials cover dominant and emerging computational neuroscience tools, how they complement one another, and specifically focus on how they can help us to better understand how the brain functions. An original component of the materials is its focus on modeling choices, i.e. how do we choose the right approach, how do we build models, and how can we evaluate models to determine if they provide real (meaningful) insight. This meta-modeling component of the instructional materials asks what questions can be answered by different techniques, and how to apply them meaningfully to get insight about brain function