University of Kassel

Protein kinase A (PKA) is a crucial signaling enzyme in neurons, with its dysregulation being implicated in neurodegenerative diseases. Assembly of the PKA holoenzyme, comprising a dimer of heterodimers of regulatory (R) and catalytic (C) subunits, ensures allosteric regulation and functional specificity. Recently, we defined the RIβ‐L50R variant as a causative mutation that triggers protein aggregation in a rare neurodegenerative disease, neuronal loss, and parkinsonism driven by a PKA mutation (NLPD‐PKA). However, the mechanism underlying uncontrolled PKA allosteric regulation and its connection to the functional outcomes leading to clinical symptoms remains elusive. In this study, we established an in vitro model using patient‐derived cells for a personalized approach and employed direct measurements of purified proteins to investigate disease mechanisms in a controlled environment. Structural analysis and circular dichroism spectroscopy revealed that cellular protein aggregation resulted from misfolded RIβ‐subunits, preventing holoenzyme assembly and anchoring through A‐kinase anchoring proteins (AKAPs). While maintaining high affinity to the C‐subunit, the resulting RIβ‐L50R:C heterodimer exhibits reduced cooperativity, requiring lower cAMP concentrations for dissociation. Consequently, there was an increased translocation of the C‐subunit into the nucleus, impacting gene expression. We successfully controlled C‐subunit translocation by introducing a mutation that decreased RIβ:C dissociation in response to elevated cAMP levels. This research thus sets the stage for developing therapeutic strategies that modulate PKA assembly and allostery, thus exerting control over the unique molecular signatures identified in the disease‐associated transcriptome profile.

Background and aims – During fieldwork in French Guiana in 2018, two fungal specimens resembling Subulicystidium oberwinkleri were collected. This study aims to clarify species- and genus-level assignment of this material and of S. oberwinkleri . Material and methods – Corticioid fruiting bodies were examined under a light microscope, and spores from the spore prints were studied morphometrically. DNA sequences of large subunit-coding DNA and internal transcribed spacer were used for maximum likelihood and Bayesian phylogenetic analyses. Furthermore, guanine-cytosine content was calculated for the LSU dataset, and UNITE Species Hypotheses Matching Analysis was performed for newly generated ITS sequences. Key results – The new genus, Palliocystidium , is introduced in the family Hydnodontaceae, based on the peculiar pattern of cystidial encrustation (crystalline plates of various shapes) and cystidial septation and supported by results of phylogenetic analyses. Within the new genus, the new species P. chlamydatum from French Guiana is described. In addition, Subulicystidium oberwinkleri is transferred to Palliocystidium . The two species can be distinguished by the size of their reniform spores. Both species display high levels of guanine-cytosine content at the scale of the order Trechisporales. Conclusions – In the newly introduced genus Palliocystidium and genera Subulicystidium and Luellia , there is significant potential for further exploration of species diversity and generic boundaries. Additional intensified fruiting-body-based sampling of taxa and genes is necessary to clarify the relationship of genera within Hydnodontaceae.

With rapid urbanization currently observed and forecasted, especially in Asia, green and blue infrastructure (GBI) has emerged as an important component of urban spaces, providing multiple ecosystem services, and augmenting human well-being. GBI promotes a better communication of ecosystem services and biodiversity conservation as well as a better prioritization, integration, and structuring of implementation strategies. A focus on GBI is particularly useful in a country like India that needs holistic approaches including multiple stakeholders and sectors to facilitate inclusive and sustainable urban planning. This book chapter developed a synthesis view that interprets outcomes in the governance and management of three GBI elements: wooded groves, a protected area, and lakes under conditions of rapid urbanization in India’s fastest growing metropolis through a set of social-ecological indicators. For these elements of local GBI in greater Bengaluru region, a snapshot of biophysical, ecological, and institutional characteristics is provided, together with an indication of the direction they have developed over time. Subsequent cross-comparative analyses identified individual and overarching trends in urbanization driven transformations of GBI. The selected cases show that urbanization leads to encroachment of GBIs, increasing the number of actor groups and changes in ecosystem services derived by people. We conclude that GBIs are often ignored by policy and planning. We advocate the need for greater attention of policymakers to consider these important elements of urban fabric especially for their contributions to societal well-being.

The present study seeks to expand the knowledge on dissimilar fusion welding of the material combination NiTi/Nb/Ti by investigating micro electron beam welding in a butt-joint configuration. In addition to adapted power modulation, a novel approach of utilizing the process-inherent fast beam oscillation is applied to improve the melting and intermixing behavior of the comparatively high-melting Nb filler material. Two different Nb thicknesses, measuring 0.2 and 0.4 mm, are implemented and compared with regard to weldability and microstructural evolution in the weld metal. It is demonstrated that the welding experiments are associated with major challenges due to the considerable differences in melting temperature and thermal conductivity of the base and filler materials, resulting in inhomogeneous elemental distribution and welding defects. Nevertheless, the welded joints exhibit excellent mechanical properties under quasi-static tensile load, which can be attributed to a reduced formation of Ti 2 Ni intermetallic compounds due to the intermixing of Nb. Ultimate tensile strengths of up to 673 MPa and elongations at break of 6.9% are achieved, demonstrating that micro electron beam welding is a promising process to produce high-strength dissimilar NiTi/Nb/Ti joints.

The underlying logics of how welfare states redistribute financial resources to their citizens have been studied intensively. Researchers have focussed on redistribution based on the principles of work, residency or taxpaying. However, family as a redistributive principle in its own right has never systematically been studied neither for a wide range of welfare regulations, nor for welfare benefits and obligations. Hence we do not know in how far the redistributive logics based on other redistributive principles are also found for the redistributive principle of the family. In this paper we address this question, using EUROMOD to analyse the degree of legally stipulated, family-related redistribution for forty-two hypothetical family forms. In our findings, all EU member-states show family-related redistribution in line with the ‘Robin Hood’ logic, with special redistribution to families with several children, single-earner families, and single parents.

Zusammenfassung Einleitung Mit dem neuen Cannabisgesetz wurde am 01.04.2024 der Konsum von Cannabis legalisiert. Bereits zuvor war Cannabis eine der am häufigsten konsumierten Drogen. Ein problematischer Konsum birgt jedoch vielfältige gesundheitliche Risiken, besonders für Jugendliche und junge Erwachsene. Die aktuelle Studie untersucht die Entwicklung des Cannabiskonsums vom Jugend- zum jungen Erwachsenenalter sowie Risiko- und Schutzfaktoren für einen problematischen Konsum bei jungen Erwachsenen. Methoden Die Daten stammen aus der deutschen Längsschnittstudie „Zukunft Familie“ (Start: 2001, 18-Jahres-Follow-up: 2020–2022). Die Stichprobe umfasst N = 278 junge Erwachsene ( M = 22,3 Jahre). Betrachtet werden Prävalenzraten und die Entwicklung des Cannabiskonsums vom Jugend- zum jungen Erwachsenenalter. Als mögliche Risiko- und Schutzfaktoren für einen problematischen Konsum werden verschiedene kind- und familienbezogene Variablen des Kindergarten- und Jugendalters untersucht. Ergebnisse Die Lebenszeitprävalenz für Cannabiskonsum betrug 57,6 %, die Prävalenz für problematischen Konsum 13,7 %. Junge Männer hatten ein 3,3-fach höheres Risiko für einen problematischen Konsum als junge Frauen und junge Erwachsene, die bei der Befragung im Jugendalter bereits Cannabis konsumiert hatten, ein 2,6-fach höheres Risiko. Als Risikofaktor für einen problematischen Konsum erwies sich primär das Ausmaß externalisierender Verhaltensauffälligkeiten im Jugendalter aus Muttersicht. Diskussion Die Ergebnisse bestätigen, dass Cannabiskonsum sowie ein problematischer Konsum bei jungen Erwachsenen bereits vor der Legalisierung kein seltenes Phänomen waren. Sie unterstreichen die Notwendigkeit für verhältnis- und verhaltenspräventive Maßnahmen und bieten zahlreiche Ansatzpunkte für die zukünftige Forschung.

In yeast, tRNA modifications that are introduced by the Elongator complex are recognized by zymocin, a fungal tRNase killer toxin that cleaves the anticodon. Based on zymocin resistance conferred by mutations in KTI12, a gene coding for an Elongator interactor, we further examined the yet vaguely defined cellular role of Kti12. Guided by structural similarities between Kti12 and PSTK, a tRNA kinase involved in selenocysteine synthesis, we identified conserved basic residues in the C-terminus of Kti12, which upon site-directed mutagenesis caused progressive loss of tRNA binding in vitro. The inability of Kti12 to bind tRNA led to similar phenotypes caused by Elongator inactivation in vivo. Consistently, tRNA binding deficient kti12 mutants drastically suppressed Elongator dependent tRNA anticodon modifications and reduced the capacity of Kti12 to interact with Elongator. We further could distinguish Elongator unbound pools of Kti12 in a tRNA dependent manner from bound ones. In summary, the C-terminal domain of Kti12 is crucial for tRNA binding and Kti12 recruitment to Elongator, which are both requirements for Elongator function suggesting Kti12 is a tRNA carrier that interacts with Elongator for modification of the tRNA anticodon.

The study addresses triaminoalkenes derived from [3]ferrocenophane‐type cyclic (alkyl)(amino)carbenes (fcCAACs) fc(CPh2CNR) (fc = 1,1′‐ferrocenylene) and N‐heterocyclic carbenes (NHCs). Stable target compounds are obtained in good yields as crystalline solids by the combination of [fc(CPh2CHNMe)][BF4] with N,N′‐dimethylimidazolin‐2‐ylidene and of [fc(CPh2CHN‐p‐C6H4‐tBu)](OTf) with 1,3,4,5‐tetramethylimidazolin‐2‐ylidene, respectively, followed by treatment of the resulting addition product with KN(SiMe3)2. Due to the presence of a triaminoethene unit and a ferrocene moiety, four redox states are expected for such fcCAAC–NHC heterodimers, viz., electroneutral, mono‐, di‐, and tricationic. An investigation of their redox behavior by electrochemical methods (cyclic voltammetry and differential pulse voltammetry) has revealed that these compounds undergo two consecutive one‐electron oxidations, with the poor stability of the dicationic species in solution preventing an observation of the tricationic redox state. A density functional theory (DFT) study shows that the highest occupied molecular orbital (HOMO) is localized on the CCN2 atom, which, in agreement with electron paramagnetic resonance results, is the site of the first oxidation. The second oxidation mainly involves the Fe atom, where the HOMO−1 is localized, resulting in a species with a triplet ground state composed, to a first approximation, of a carbon‐centered and an iron‐centered radical.

Landscapes are places where multiple social-ecological relations thrive. However, due to intensification of industrial land-uses, they are losing their diversity of species and functions, languages and practices, thereby influencing the ways in which people interact with each other and non-human beings across the globe. A better understanding of such changes in landscapes is necessary to enhance urgent transformative change to overcome the sustainability crisis that humans and non-humans are currently facing. In this article, using an in-depth, reflexive thematic qualitative approach, we characterised landscape homogenisation across five case study landscapes in Ethiopia, Finland, Germany, Iran and Uruguay by a) identifying and describing the main driving forces underpinning landscape homogenisation within each landscape and b) exploring and discussing some of the main relations between different driving forces contributing to landscape homogenisation across landscapes. Four main driving forces characterising and contributing to landscape homogenisation globally emerged from the results: economic growth imperative; industrialised commodity production; rural depopulation; and abandonment of traditional practices. While all forces were observed across all studied landscapes, they took different shapes and ways in each context. We provide an operational conceptualisation of landscape homogenisation, highlight that the loss of landscape heterogeneity is driven by a complex fabric of co-occurring driving forces, and discuss potential constraints for transformative change. Our approach and lessons learned can provide insights to inform action-oriented research in other rural landscapes globally to addressing the interwoven nature of the issues challenging landscapes’ sustainability.

Over the past century, the inefficient use of reactive nitrogen (Nr) has raised concerns regarding global food production and planetary sustainability. This study investigates nitrogen (N) losses in tomato production near Kabul, Afghanistan, aiming to improve nitrogen use efficiency (NUE) for enhanced food security and environmental protection. Three fertilizer treatments were tested: (A) animal manure + ¼ dose of chemical fertilizer, (B) night soil + ¼ dose of chemical fertilizer, and (C) full dose of chemical fertilizer, with sub-treatments varying in N application (25% less, 25% excess, and farmers’ practice). A no-fertilizer control treatment was included. Nitrogen losses through ammonia emissions and nitrate–N leaching were monitored, while nitrogen balances and NUE were calculated. The findings revealed that ammonia emissions decreased by 33% in treatment A2 and by 30% in treatment B3 compared to surface application. However, nitrate–N leaching peaked at 145 kg N ha⁻¹ in A2 and 128 kg N ha⁻¹ in B3, with positive N balances observed across treatments, the highest being 300 kg N ha⁻¹ in treatment A. NUE ranged from 30% (A and B) to 55% (control), highlighting the widespread overapplication of N in Afghan agriculture. This study demonstrates that efficient N management practices can reduce environmental losses while maintaining tomato yield, offering a novel pathway toward sustainable farming in the region.

Aquatic fungi play a key role in the turnover of organic matter in freshwater ecosystems, such as leaf litter in streams. Even though agriculturally applied fungicides that reach streams through spray drift or surface runoff may endanger the important functions of these organisms, potential effects of fungicides on the diversity of a complex fungal community are still understudied. We used metabarcoding of fungal DNA to investigate composition changes in a natural leaf litter associated aquatic mycobiome in artificial stream channels and flasks treated with 250 µg/L of the fungicide penconazole. Treated samples were compared with control samples from untreated systems and samples from a reference stream over 21 days. Our results show that differences in community composition between fungicide treated and control samples were weak for leaves that were pre-conditioned for two weeks in the reference stream prior to exposure. Apart from treatment effects on fungal biomass (in terms of ergosterol content), only the read numbers of two key taxa indicated an abundance shift that was probably induced by the fungicide. In contrast, strong diversity effects were observed during the following long-term recolonization (85 days) of sterilized leaves under penconazole stress, in which the occurrences of key taxa were significantly reduced in fungicide treated stream channels. Our results imply that DNA metabarcoding can be particularly effective to detect changes in fungal communities during the colonization of leaf litter, a crucial process for the following decomposition and the conservation of fungal diversity.

This study examines the consumer response to (1) pricing and discounts, (2) packaging design, and (3) sustainability‐enhancing technology and apps on special offers before the maximum shelf life expires. A survey of 303 consumers currently living in Germany supports the relevance of these factors. Consumer attitudes toward sustainability moderate the relationship of pricing and discounts as well as that of technology and apps to consumer responses. Most notably, by consolidating identifying factors influencing food waste at the retail level and the influence of consumer behavior and attitudes toward sustainability into a holon flux, we introduce the concept of sustainability holons embedded in the context of feedback loops and food waste, taking the sustainable development perspectives. The study's exploration of holons and holon flux highlights the need for future research to focus on varying levels of granularity in divergent industries, which could enhance the precision and applicability of sustainability holons in diverse cultural and business contexts and strengthen stakeholder engagement.

Diphthamide is a post-translationally modified histidine residue of eukaryotic TRANSLATION ELONGATION FACTOR 2 (eEF2) and the target of diphtheria toxin in human cells. In yeast and mammals, the 4Fe-4S cluster-containing proteins Dph1 and Dph2 catalyze the first biosynthetic step of diphthamide formation. Here, we identify Arabidopsis (Arabidopsis thaliana) DPH2 and show that it is required for diphthamide biosynthesis, localizes to the cytosol and interacts physically with AtDPH1. Arabidopsis dph2 mutants form shorter primary roots and smaller rosettes than the wild type, similar to dph1 mutants which we characterized previously. Additionally, increased ribosomal -1 frameshifting error rates and attenuated TARGET OF RAPAMYCIN (TOR) kinase activity in dph2 mutants also phenocopy the dph1 mutant. Beyond the known heavy-metal hypersensitivity and heat shock tolerance of dph1, we show here that both dph1 and dph2 mutants are hypersensitive to elevated light intensities and oxidative stress, and that wild-type Arabidopsis seedlings accumulate diphthamide-unmodified eEF2 under oxidative stress. Both mutants share the deregulation of 1,186 transcripts associated with several environmental and hormone responses. AtDPH1 and AtDPH2 do not complement the corresponding mutants of Saccharomyces cerevisiae. In summary, DPH2 and DPH1 interact to function inter-dependently in diphthamide formation, the maintenance of translational fidelity, wild-type growth rates and TOR kinase activation, and they contribute to mitigating damage from elevated light intensities and oxidative stress. Under oxidative stress, a dose-dependent loss of diphthamide could potentiate downstream effects in a feed-forward loop. This work advances our understanding of translation and its interactions with growth regulation and stress responses in plants.

Topographical as well as microscopic imaging of nanoscale surfaces plays a pivotal role across various disciplines. Nevertheless, achieving fast, label-free, and accurate characterization of laterally expanded structures below the diffraction limit remains challenging. Recent studies highlight the use of microsphere assistance for resolution improvement. Confocal, conventional, and interference microscopy, augmented by microspheres, enable the imaging of small structures that were previously inaccessible. In this contribution, results of microsphere-assisted confocal and conventional bright-field microscopy (MAM) are compared to underline the decisive role of the confocal effect. Furthermore, an extensive comparison of simulated confocal results is presented to highlight the experimental results.