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Abstract Contact-dependent growth inhibition (CDI) is a wide-spread mechanism of inter-bacterial competition. CDI+ bacteria deliver CdiA-CT toxins into neighboring bacteria and produce specific immunity proteins that protect against self-intoxication. The CdiA-CT toxin from uropathogenic Escherichia coli 536 is a latent tRNase that is only active when bound to the cysteine biosynthetic enzyme CysK. Remarkably, the CysK:CdiA-CT binding interaction mimics the ‘cysteine synthase’ complex of CysK:CysE. The C-terminal tails of CysE and CdiA-CT each insert into the CysK active-site cleft to anchor the respective complexes. The dissociation constant for CysK:CdiA-CT (K d ~ 11 nM) is comparable to that of the E. coli cysteine synthase complex (K d ~ 6 nM), and both complexes bind through a two-step mechanism with a slow isomerization phase after the initial encounter. However, the second-order rate constant for CysK:CdiA-CT binding is two orders of magnitude slower than that of the cysteine synthase complex, suggesting that CysE should outcompete the toxin for CysK occupancy. However, we find that CdiA-CT can effectively displace CysE from pre-formed cysteine synthase complexes, enabling toxin activation even in the presence of excess competing CysE. This adventitious binding, coupled with the very slow rate of CysK:CdiA-CT dissociation, ensures robust nuclease activity in target bacteria.

Abstract The KATRIN experiment aims to determine the neutrino mass scale with a sensitivity of 200 $${\mathrm{meV}/\mathrm{c}^2}$$ meV / c 2 (90% C. L.) by a precision measurement of the shape of the tritium $$\beta $$ β -spectrum in the endpoint region. The energy analysis of the decay electrons is achieved by a MAC-E filter spectrometer. To determine the transmission properties of the KATRIN main spectrometer, a mono-energetic and angular-selective electron source has been developed. In preparation for the second commissioning phase of the main spectrometer, a measurement phase was carried out at the KATRIN monitor spectrometer where the device was operated in a MAC-E filter setup for testing. The results of these measurements are compared with simulations using the particle-tracking software “Kassiopeia”, which was developed in the KATRIN collaboration over recent years.

Beyond the functional tasks that assistance dogs are trained for, there is growing literature describing their benefits on the psychosocial health and wellbeing of their handlers. However, this research is not only widely disparate but, despite its growth, has not been reviewed since 2012. Our objective was to identify, summarize, and methodologically evaluate studies quantifying the psychosocial effects of assistance dogs for individuals with physical disabilities. Following PRISMA guidelines, a systematic review was conducted across seven electronic databases. Records were independently screened by two authors. Studies were eligible for inclusion if they assessed outcomes from guide, hearing, medical, or mobility service dogs, if they collected original data on handlers' psychosocial functioning, and if the outcome was measured quantitatively with a validated, standardized measure. Studies on psychiatric service dogs, emotional support dogs, and pet dogs were excluded. Of 1,830 records screened, 24 articles were identified (12 publications, 12 theses) containing 27 studies (15 cross-sectional, 12 longitudinal). Studies assessed the effects of mobility (18), hearing (7), guide (4), and medical (2) assistance dog partnerships with an average sample size of N = 83. An analysis of 147 statistical comparisons across the domains of psychological health, quality of life, social health, and vitality found that 68% of comparisons were null, 30% were positive in the hypothesized direction, and 2% were negative. Positive outcomes included significant effects of having an assistance dog on psychological wellbeing, emotional functioning, self-esteem, and vitality. However, it is of note that several methodological weaknesses of the studies make it difficult to draw any definitive conclusions, including inadequate reporting and a failure to account for moderating or confounding variables. Future research will benefit from stronger methodological rigor and reporting to account for heterogeneity in both humans and assistance dogs as well as continued high-quality replication.

Glucocorticoids (GCs) act via the glucocorticoid receptor (NR3C1, GRα) to combat overshooting responses to infectious stimuli, including lipopolysaccharide (LPS). As such, GCs inhibit the activity of downstream effector cytokines, such as tumor necrosis factor (TNF). PPARα (NR1C1) is a nuclear receptor described to function on the crossroad between lipid metabolism and control of inflammation. In the current work, we have investigated the molecular mechanism by which GCs and PPARα agonists cooperate to jointly inhibit NF-κB-driven expression in A549 cells. We discovered a nuclear mechanism that predominantly targets Mitogen- and Stress-activated protein Kinase-1 activation upon co-triggering GRα and PPARα. In vitro GST-pull down data further support that the anti-inflammatory mechanism may additionally involve a non-competitive physical interaction between the p65 subunit of NF-κB, GRα, and PPARα. Finally, to study metabolic effector target cells common to both receptors, we overlaid the effect of GRα and PPARα crosstalk in mouse primary hepatocytes under LPS-induced inflammatory conditions on a genome-wide level. RNA-seq results revealed lipid metabolism genes that were upregulated and inflammatory genes that were additively downregulated. Validation at the cytokine protein level finally supported a consistent additive anti-inflammatory response in hepatocytes.

Wicked socio-ecological problems are inherently complex and require an interdisciplinary approach for mitigation. Here, we investigated the many drivers of human-lion conflict in East Africa and present a novel conceptual model illustrating the intricate interactions within and between the five main dimensions of conflict. We highlight the importance of broadening research efforts to include these multiple dimensions at all stages of the research process as well as to incorporate higher levels of diversity into research teams. We offer examples and recommendations on how to approach human-lion conflict from a more interdisciplinary perspective. However, challenges exist and will continue to arise as diverse interdisciplinary teams form. We address several main barriers to interdisciplinarity and encourage researchers and institutions to support a team science approach to solving wicked problems like human-lion conflict.

Submarine groundwater discharge (SGD) is a ubiquitous source of meteoric fresh groundwater and recirculating seawater to the coastal ocean. Due to the hidden distribution of SGD, as well as the hydraulic- and stratigraphy-driven spatial and temporal heterogeneities, one of the biggest challenges to date is the correct assessment of SGD-driven constituent fluxes. Here, we present results from a 3-dimensional seasonal sampling campaign of a shallow subterranean estuary in a high-energy, meso-tidal beach, Spiekeroog Island, Northern Germany. We determined beach topography and analyzed physico-chemical and biogeochemical parameters such as salinity, temperature, dissolved oxygen, Fe(II) and dissolved organic matter fluorescence (FDOM). Overall, the highest gradients in pore water chemistry were found in the cross-shore direction. In particular, a strong physico-chemical differentiation between the tidal high water and low water line was found and reflected relatively stable in- and exfiltrating conditions in these areas. Contrastingly, in between, the pore water compositions in the existing foreshore ridge and runnel system were very heterogeneous on a spatial and temporal scale. The reasons for this observation may be the strong morphological changes that occur throughout the entire year, which affect the exact locations and heights of the ridge and runnel structures and associated flow paths. Further, seasonal changes in temperature and inland hydraulic head, and the associated effect on microbial mediated redox reactions likely overprint these patterns. In the long-shore direction the pore water chemistry varied less than the along the cross-shore direction. Variation in long-shore direction was probably occurring due to topography changes of the ridge-runnel structure and a physical heterogeneity of the sediment, which produced non-uniform groundwater flow conditions. We conclude that on meso-tidal high energy beaches, the rapidly changing beach morphology produces zones with different approximations to steady-state conditions. Therefore, we suggest that zone-specific endmember sampling is the optimal strategy to reduce uncertainties of SGD-driven constituent fluxes.