This article scrutinizes linking social capital formation between informal civil society and local administrations during and after the 2015 European refugee reception crisis. Drawing from 61 semi-structured interviews with members of civil society organizations and local administrations in two German cities, this study documents that the production of linking social capital is by no means guaranteed. Structural power asymmetries and different logics of action between volunteers and local administrative officials regularly create tensions that can serve as relational breaking points. Accepting these inherent tensions and creating platforms to work things out against the odds are essential to produce trustful and responsive relationships.

A large number of studies have been conducted on the structure of Intellect, which is one of the facets of Openness/Intellect. However, far less is known about the development of Intellect and the impact of external influences such as critical life events. In the present study, we investigated socialization and selection effects of Intellect in relation to the subjective perception of life events and self-efficacy. In a large German longitudinal sample of adolescents and emerging adults ( N = 1477), we used mixed linear models to assess mean-level changes and moderating effects across three measurement occasions. We found significant change in Intellect but no evidence of the influence of experiencing a critical life event. Self-efficacy predicted mean levels and change over time in Intellect yet did not interact with perceptions of life events. Further research ideas are discussed.

Schließt eine Gesellschaft zur Absicherung des persönlichen Haftungsrisikos ihrer Unternehmensleiter eine D&O-Versicherung ab, so stellt sich in verschiedenem Kontext die Frage, inwieweit ihr das Wissen natürlicher Personen – insbesondere: versicherter Personen – zugerechnet werden kann. Der Beitrag bietet zunächst einen Überblick zu den gesellschaftsrechtlichen Grundregeln der Wissenszurechnung. Sodann werden die Auswirkungen auf die D&O-Versicherung anhand zweier Praxisfragen erörtert, nämlich der Rückwärtsdeckung und des Ausschlusses für wissentliche Pflichtverletzungen. Der Beitrag gelangt zu dem Ergebnis, dass die Wissenszurechnung zur Gesellschaft als der Versicherungsnehmerin in bestimmten Fällen auch einer unwissenden versicherten Person schaden kann, es sei denn, es geht um einen an einen individuellen Verschuldensvorwurf anknüpfenden Verhaltensverstoß. Hinsichtlich des Ausschlusses wissentlicher Pflichtverletzungen ist danach zu differenzieren, ob teils wissentlich, teils fahrlässig begangene Pflichtverletzungen von ein und derselben oder von mehreren versicherten Personen zu verantworten sind.

Plasma cells provide protective antibodies following an infection or vaccination. A network of intrinsic and extrinsic factors fine-tunes the generation of a heterogenous plasma cell pool with varying metabolic requirements, transcriptional profiles and lifespans. Among these, the B cell maturation antigen (BCMA) has been implicated in the APRIL-mediated survival of long-lived plasma cells. To characterize the terminal maturation of plasma cells, we constructed a BCMA reporter mouse (BCMA:Tom) that exclusively labeled antibody-secreting cells and revealed that BCMA:Tom expression varied by IgH isotype and increased with plasma cell maturity. The BCMA reporter, used alongside the Blimp1-GFP reporter, also allowed detailed tracking of plasma cell development and highlighted the importance of the in vivo microenvironment to complete plasma cell maturation. Therefore, the BCMA:Tom reporter mouse provides a valuable tool for tracking plasma cell development and maturation with flow cytometry or advanced imaging techniques, enabling a deeper understanding of the mechanisms regulating plasma cell heterogeneity and longevity.

Background

Previous data indicated that the leucine-rich α-2 glycoprotein 1 (LRG1) pathway contributes to vascular dysfunction during cancer growth. Therapeutic targeting of LRG1 normalized tumor vessel dysfunction and enhanced the efficacy of anti-cancer adoptive T cell therapy. A major clinical problem after allogeneic hematopoietic stem cell transplantation (alloHSCT) and after chimeric antigen receptor (CAR) T-cell therapy is the induction of hyperinflammatory side effects, which are typically associated with severe endothelial dysfunction.

Methods

We investigated LRG1 in preclinical models and in patient samples.

Results

In prospective studies, we found elevated LRG1 serum levels in patients with cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome after CAR-T-cell therapy as well as in patients with acute graft-versus-host disease (aGVHD) after alloHSCT. In preclinical models of aGVHD, we found vasculature-associated LRG1 upregulation as well as LRG1 pathway gene upregulation. The genetic deletion of LRG1 in alloHSCT donors and in alloHSCT recipients led to reduced clinical and histological aGVHD. In line with this, LRG1 deletion led to clinically and histologically reduced disease severity in experimental inflammatory models of colitis (dextran sulfate sodium colitis) and paw edema. LRG1 deletion reduced inflammation-related vascular leakiness, endothelial cell proliferation, and migration.

Conclusions

The current data support the hypothesis that LRG1 is an attractive therapeutic target after alloHSCT and after CAR-T cell therapy for cancer because of its role in dysfunctional tumor vessels as well as in inflammatory complications.

Introduction: Genetic manipulation of murine retinal tissue through ocular administration of adeno-associated viruses (AAVs) has become a standard technique to investigate a multitude of mechanisms underlying retinal physiology. Resultantly, developments of recombinant viral vectors with improved transduction efficiency and further methodological improvements have mostly focused on murine tissue, whereas AAVs successfully targeting avian retinae have remained scarce.

Methodology: Using a custom-designed injection setup, we identified a viral serotype with the capability to successfully induce widespread transduction of the bird retina.

Results: Intravitreal administration of an AAV type 2/9 encoding for enhanced green fluorescent protein (EGFP) in night-migratory European robins (Erithacus rubecula) resulted in transduction coverages of up to 60% within retinal tissue. Subsequent immunohistochemical analyses revealed that the AAV2/9-EGFP serotype almost exclusively targeted photoreceptors: rods, various single cones (UV, blue, green, and red cones), and both (accessory and principal) members of double cones.

Discussion: The consistently high and photoreceptor-specific transduction efficiency makes the AAV2/9 serotype a powerful tool for carrying out genetic manipulations in avian retinal photoreceptors, thus opening a wealth of opportunities to investigate physiological aspects underlying retinal processing in birds, such as physiological recordings and/or post-transductional behavioural readouts for future vision-related research.

We present a protocol for micro-endoscopic fluorescence lifetime imaging in the femoral marrow of mice allowing the analysis of NAD(P)H-dependent metabolism at single cell level, in vivo . Therefore, we employed a gradient refractive index (GRIN) lens system fixed to the mouse femur by a specialized implant. We provide step-by-step instructions for the practical usage of the microendoscopic femoral implant and discuss experimental parameters required for reliable NAD(P)H FLIM analysis, particularly referring to photon statistics and signal-to-noise ratio. Representative results indicate metabolic heterogeneity both in marrow tissue environment and among marrow LysM + myeloid cells in vivo . We expect the here presented microendoscopic FLIM approach to enable the analysis of cellular functions and dysfunctions, beyond cellular metabolism, providing a better understanding of bone biology, in health and disease.

Several different types of light-absorbing particles (LAPs) darken snow surfaces, enhancing snowmelt on glaciers and snowfields. LAPs are often present as a mixture of biotic and abiotic components at the snow surface, yet methods to separate their respective abundance and albedo-reducing effects are lacking. Here, we present a new optimisation method enabling the retrievals of dust, black carbon, and red algal abundances and their respective darkening effects from spectral albedo. This method includes a deep-learning emulator of a radiative transfer model (RTM) and an inversion algorithm. The emulator alone can be used as a fast and lightweight alternative to the full RTM with the possibility to add new features, such as new light-absorbing particles. The inversion method was applied to 180 ground field spectra collected on snowfields in southern Norway, with a mean absolute error on spectral albedo of 0.0056, and surface parameters that closely matched expectations from qualitative assessments of the surface. The emulator predictions of surface parameters were used to quantify the albedo-reducing effect of algal blooms, mineral dust, and dark particles represented by black carbon. Among these 180 surfaces, the albedo reduction due to light-absorbing particles was highly variable and reached up to 0.13, 0.21, and 0.25 for red algal blooms, mineral dust, and dark particles respectively. In addition, the effect of a single LAP was attenuated by the presence of other LAPs by up to 2–3 times. These results demonstrate the importance of considering the individual types of light-absorbing particles and their concomitant interactions for forecasting snow albedo.

Feminist media research has provided a wide range of studies exploring how individuals navigate and negotiate their identities within the neoliberal platform economy. Popular feminist ideas and social media representations are often criticized for their lack of diversity and strong focus on Western, white, able-bodied, upper-class ciswomen. In this article, we expand on existing literature by focusing on creators’ self-representations under the #mixedgirlcheck on TikTok. The nomenclature of #mixedgirlcheck implies to present a different form of girlhood (‘mixed’) with the potential to subvert popular femininity. Through critical discourse analysis, we analysed 100 TikTok videos to answer our research question: ‘How do creators represent their identities in videos posted under the #mixedgirlcheck on TikTok?’. Our analysis revealed four prominent patterns in this trend: (1) the embodied performance of ‘mixed’ heritage, (2) negotiating embodied ruptures in normative authenticity and belonging, (3) embodied heterosexual performativity and the idealization of the bourgeois family and (4) capitalizing on the performance of embodied individuality. We discuss how TikTok's neoliberal platform logic rewards performances of the ‘mixed girl’ that cater to a white, heterosexual, cisgender dominant gaze, uncritical of discriminatory structures such as racism, sexism or heteronormativity. This paper contributes to platform studies by critically examining how TikTok's neoliberal platform logic shapes and rewards identity performances under #mixedgirlcheck, revealing both its reinforcement of dominant discriminatory structures and its affordances for momentary ruptures in hegemonic discourses on ‘mixed’ girlhood.

In humans, mothers and infants often engage in face‐to‐face interactions, which are often considered crucial for the social transmission of information and the typical social and cognitive development of infants. In this study, we used a comparative developmental perspective to provide an assessment of mother–infant face‐to‐face interactions in several great and small ape species and to better understand which aspects of face‐to‐face interactions are shared by humans with other species. We conducted longitudinal behavioral observations on 48 mother–infant pairs from five different genera (i.e., Hylobates : N = 9; Homo : N = 10; Nomascus : N = 6; Pan : N = 18; Symphalangus : N = 5), when infants were 1, 6, and 12 months old. Generalized linear mixed models revealed differences across ape genera and through development in the probability that mothers and infants engaged in face‐to‐face interactions during the first year of the offsprings’ life. As predicted, these interactions were more likely when mothers and infants spent less time in physical contact, in communities usually characterized by more distal parenting styles (i.e., WEIRD humans), and when infants became older and thus motorically more independent. Overall, our findings suggest that face‐to‐face interactions were likely present in the common ancestor of humans and small apes, and likely serve a similar function across ape species.

The use of timber harvesting and skidding machines significantly alters a catchment's hydrological processes due to soil compaction effects. Although it is obvious that the use of heavy forest machines increases surface runoff and water yield, quantifying these effects remains challenging. This research aimed at exploring how physically based hydrological models are suited for investigating the effects of soil compaction on hydrologic responses at the catchment scale. We employed a process‐based SWAT+ hydrological model to assess the impact of temporary (e.g., skid trails) and more permanent timber harvest infrastructure on the hydrologic response of the Palatinate Forest Biosphere Reserve in Germany. We specifically analysed the role of soil compaction in hydrological processes by simulating water fluxes under three scenarios: uncompacted soil (baseline), compacted soil during harvest and skidding operations (Scenario‐1) and due to permanently constructed infrastructures (Scenario‐2). Results demonstrated substantial alterations in water fluxes under Scenarios‐1 and ‐2 compared to the baseline, with annual average surface runoff increasing by 74% and 125%, respectively, and lateral flow decreasing by 14% and 26%. These changes varied notably between steep and low slope areas. Steep slope regions exhibited significantly larger increases in surface runoff, while low slope areas experienced greater reductions in lateral flow and percolation. This differentiation underlines the combined influence of management scenarios and slope, highlighting the critical need for forest harvesting strategies that account for spatial variability and the types of machinery employed.

The epidermal growth factor (EGF) receptor is commonly targeted in cancer therapy because it is overexpressed in many malignant cells. However, a general problem is to couple the targeting moieties and the drug molecules in a way that results in a homogeneous product. Here, we overcome this issue by engineering a variant of EGF with a single conjugation site for coupling virtually any payload. The recombinant EGF variant K‐EGFRR was expressed in E. coli Rosetta with a 4–6 mg/L yield. To confirm the accessibility of the introduced functional group, the ligand was equipped with a sulfo‐cyanine dye with a loading of 0.65 dye per ligand, which enables tracking in vitro. The kinetics and affinity of ligand–receptor interaction were evaluated by enzyme‐linked immunosorbent assay and surface plasmon resonance. The affinity of K‐EGFRR was slightly higher when compared to the wild‐type EGF (KD: 5.9 vs. 7.3 nM). Moreover, the ligand–receptor interaction and uptake in a cellular context were evaluated by flow cytometry and quantitative high‐content imaging. Importantly, by attaching heterobifunctional polyethylene glycol linkers, we allowed orthogonal click‐conjugation of the ligand to any payload of choice, making K‐EGFRR an ideal candidate for targeted drug delivery.

Vegetation fires have become increasingly recognized as a potential entrainment mechanism for mineral dust. However, the global importance of this emission pathway remains largely unknown. Based on previous LES investigations, we developed a parameterization that relates the dust emission potential of wildfires to observational data of the fire radiative power and further soil‐surface conditions. It was implemented into the aerosol‐climate model ICON‐HAM and simulations with and without the new emission pathway were conducted for the 10‐year period 2004–2013. Fire‐dust emissions can account for around 230 (190–255) Tg yr −1 , which represents around 18 (15–21) % of the total global dust emissions. These additional emissions originate largely from regions that are typically not known as significant sources of mineral dust. Locally, wildfires can enhance the presence of atmospheric dust particles and on the Southern hemisphere might even surpass other forms of dust emission. Highly dust active fire regions are identified in areas where burning grasslands create suitable emission conditions together with emissive soil types despite rather weak fires, for example, in Eastern Europe or the Central US. Fire‐dust emissions are subject to a strong seasonal cycle, mainly driven by the fire activity, following the hemispheric warm and dry seasons. Multi‐year comparisons with (dust) AOD observations revealed improvements due to the additional fire‐dust emissions, particularly in the most fire‐active regions on the Southern hemisphere. Nevertheless, further research and improvements of the parameterization are required to better classify the source areas and their variation with the changing climate and land use conditions.

Therapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer‐protein interaction. We deployed limited proteolysis mass spectrometry (LiP‐MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon‐α2a (IFN). Target conjugates were digested with the specific protease trypsin and a “heavy” 15 N‐IFN wild type (IFN‐WT) for time‐resolved quantification of the cleavage dynamics. Interactions between IFN‐α2a and its high‐affinity receptor were detailed by LiP‐MS. Then, 10 kDa polymers of PEG, linear polyglycerol (LPG), and poly(2‐oxazoline) (POX) with two different cyclooctyne linkers (BCN/DBCO) were used for site‐specific bioconjugation to azide functionalized IFN‐α2a. Tryptic events at each cleavage site and in different structural environments (loops/helices) were compared. PEG and LPG were similar, and POX showed a reduced interaction profile with the IFN‐α2a surface. All‐atom molecular dynamics simulations of IFN‐DBCO‐polymer conjugates revealed distinct and transient (below 50 ns) protein‐interaction profiles for PEG, LPG, and POX. Cleavage dynamics of IFN‐polymer conjugates from the BCN handle were homogeneous, pointing to a more conserved IFN structure than DBCO‐polymer conjugates. In summary, time‐resolved LiP‐MS for quantification of cleavage events enhances the structural understanding of transient IFN‐polymer interactions, which may be extended to other bioconjugate types.

We report hitherto elusive side‐on η2‐bonded palladium(0) carbonyl (anthraquinone, benzaldehyde) and arene (benzene, hexafluorobenzene) palladium(0) complexes and present the catalytic hydrodefluorination of hexafluorobenzene by cyclohexene. The comparison with respective cyclohexene, pyridine and tetrahydrofuran complexes reveals that the experimental ligand binding strengths follow the order THF<C6H6<C6F6<cyclohexene<pyridine<benzaldehyde<anthraquinone. To understand this surprising order, the complexes’ electronic structures were elucidated by nuclear magnetic resonance (NMR), single crystal X‐Ray diffraction (sc‐XRD), ultraviolet/visible (UV/Vis) electronic absorption, infrared (IR) vibrational, Pd L3‐edge X‐ray absorption (XAS), and X‐ray photoelectron (XP) spectroscopic techniques, complemented by Density Functional Theory (DFT) calculations including energy decomposition (EDA‐NOCV) and effective oxidation state (EOS) analyses. For benzene, pyridine and cyclohexene, bonding follows the donor/acceptor picture of the Dewar–Chatt–Duncanson model. In stark contrast, hexafluorobenzene, benzaldehyde and anthraquinone bind via essentially the π‐channel only and thus as π‐analogues of Z‐acceptor ligands. This contribution elucidates the control of functional‐group selectivity in palladium(0) catalysis and delineates a novel strategy to activate electron‐deficient π‐systems.

The zona glomerulosa (ZG) synthesizes the mineralocorticoid aldosterone. The primary role of aldosterone is the maintenance of volume and electrolyte homeostasis. Aldosterone synthesis is primarily regulated via tightly controlled oscillations in intracellular calcium levels in response to stimulation. It has previously been shown that calcium oscillations are synchronized through mechanical linkage between adjacent ZG cells. In many other cell types, similar synchronization is rather dependent on gap junctions (GJ). The recent discovery of mutations in CADM1 was linked to impaired GJ function in the ZG. Based on published transcriptomics data, we re‐examined the presence and functional impact of GJ in the ZG. We found evidence for the expression of murine connexin 43 and 37 using microarray data, in‐situ hybridization and immunohistology. Connexin 43 was also present in human samples. Calcium oscillations in ZG rosettes showed some degree of synchronization as reported previously. Unspecific GJ inhibition only had a small impact on this synchronicity. However, no signs of connections between cytosols could be observed as indicated by the lack of fluorescence recovery after photobleaching. We conclude that, while connexin proteins are expressed in the ZG, functional GJ in the physiological ZG are rare and of little consequence for calcium signaling.

Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD). However, the pathogenesis of CVD in CKD remains incompletely understood. Endothelial extracellular vesicles (EC‐EVs) have previously been associated with CVD. We hypothesized that CKD alters EV release and cargo, subsequently promoting vascular remodelling. We recruited 94 children with CKD, including patients after kidney transplantation and healthy donors, and performed EV phenotyping and functional EV analyses in the absence of age‐related comorbidities. Plasma EC‐EVs were increased in haemodialysis patients and decreased after kidney transplantation. Thirty microRNAs were less abundant in total CKD plasma EVs with predicted importance in angiogenesis and smooth muscle cell proliferation. In vitro, CKD plasma EVs induced transcriptomic changes in angiogenesis pathways and functionally impaired angiogenic properties, migration and proliferation in ECs. High shear stress, as generated by arterio‐venous fistulas, and uremic toxins were considered as potential drivers of EV release, but only the combination increased EV generation from venous ECs. The resulting EVs recapitulated miRNA changes observed in CKD in vivo. In conclusion, CKD results in the release of EVs with altered miRNA profiles and anti‐angiogenic properties, which may mediate vascular pathology in children with CKD. EVs and their miRNA cargo may represent future therapeutic targets to attenuate CVD in CKD.

Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available. Cell‐surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development. We present a method to synthesize LPS substructures, covering over 70 % of virulent KP strains that were used to characterize the antibody repertoire of infected patients. Thereby, glycoconjugate vaccine leads against the Klebsiella pneumoniae serotypes O1, O2a, O2afg and O2ac have been identified.

Energy transfer catalysis (EnT) has had a profound impact on contemporary organic synthesis enabling the construction of higher in energy, complex molecules, via efficient access to the triplet excited state. Despite this, intermolecular reactivity, and the unique possibility to access several reaction pathways via a central triplet diradical has rendered control over reaction outcomes, an intractable challenge. Extended chromophores such as non‐symmetrical dienes have the potential to undergo [2+2] cycloaddition, [4+2] cycloaddition or geometric isomerisation, which, in combination with other mechanistic considerations (site‐ and regioselectivity), results in chemical reactions that are challenging to regulate. Herein, we utilise boron as a tool to probe reactivity of non‐symmetrical dienes under EnT catalysis, paying particular attention to the impact of boron hybridisation effects on the target reactivity. Through this, a highly site‐ and regioselective [2+2] cycloaddition was realised with the employed boron motif effecting reaction efficiency. Subtle modifications to the core scaffold enabled a [4+2] cycloaddition, while a counterintuitive regiodivergence was observed in geometric isomerisation versus [2+2] cycloaddition. The observed reactivity was validated via a mechanistic investigation, determining the origin of regiodivergence and reaction selectivity in competing EnT processes.