Hochschule Bielefeld

Absence of the endosomal SNAREs vti1a and vti1b results in perinatal death and severe neuronal phenotypes in mice, while lack of one of these proteins results in minor phenotypes. Proteomic differences were investigated to obtain a deeper insight into processes in which vti1a and vti1b are involved. Here we applied a bottom-up shotgun proteomic approach to investigate the differences in wild-type, double heterozygous (DHET), vti1a-/- vti1b-/- double knockout (DKO), vti1a-/- knockout and vti1b-/- knockout cerebral cortices. Single deletions did not affect protein levels significantly. A total of 1725 proteins were detected of which 69 were less abundant and 191 proteins were more abundant in DKO cortices. Many less abundant proteins belonged to cellular components and reactome pathways synapse, synaptic vesicle cycle, vesicle mediated transport, L1CAM interaction, and cholesterol biosynthesis in pathway enrichment analysis. More abundant proteins were enriched in cellular components and Kyoto Encyclopaedia of Genes and Genomes (KEGG)-pathways such as spliceosome, ribosome, carbon metabolism, and ribonucleoprotein complex. Immunoblotting validated reduced expression levels of the tested synaptic vesicle proteins as well as increased amounts of lysophosphatidylcholine acyltransferase 1 (Lpcat1) and neuron-specific gene 2 (Nsg2), which is involved in postsynaptic AMPA-receptor recycling. These data indicate that the synapse and cell adhesion were strongly affected in DKO brains. STATEMENT OF SIGNIFICANCE OF THE STUDY: Distinct populations of neurons and glia cells are generated and organize into layers during brain development. Neurons develop an elaborate morphology to transmit information via axons and synapses to dendrites in receiving neurons. These neurites form via several specialized pathways of vesicle secretion and endocytosis. Fusion between these membranes requires members of the SNARE protein family. Double knockouts of the endosomal SNAREs vti1a and vti1b (DKO) result in perinatal lethality in mice with massive defects in the brain. In this study we compared the proteome of DKO brain cortices with double heterozygous controls to obtain insights into the molecular alterations and affected pathways. DKO brains contained lower amounts of synaptic proteins and proteins involved in cell adhesion, membrane trafficking and cholesterol biosynthesis. Several proteins of spliceosomes, ribosomes and carbon metabolism were more abundant in DKO brains, which may be a consequence of the reduced amounts of synaptic proteins or a shift in cell populations. Lysophosphatidylcholine acyltransferase 1 (Lpcat1) and neuron-specific gene 2 (Nsg2), which is involved in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) recycling, were confirmed to be more abundant by Western blotting. These data point to defects in trafficking especially in the synapse and in cell adhesion, which is required for neurite outgrowth.

This work-in-progress paper addresses the transition gap between visual, text-based, and complex programming skills in early computer science education. We present a multi-level workshop concept designed to provide a coherent and motivating learning progression across different programming stages. The workshops integrate narrative-driven gameplay with progressively challenging programming tasks in a custom-developed 2D dungeon crawler framework, aiming to support learners in progressing from block-based coding to text-based and open code manipulation. The concept was implemented in collaboration with regional schools and industry partners and evaluated in six workshops with 92 participants. Initial results from pre- and post-surveys indicate high acceptance and a positive trend in programming interest, particularly among female students.

Purpose The aim of this research was to synthesize the literature on workplace outcomes of gender diversity in sport leadership using a realist synthesis approach, helping to reduce stakeholders’ uncertainty regarding potential consequences of increased gender diversity. Design/methodology/approach The articles were identified using rapid evidence assessment (n = 24) and synthesized in terms of adopted theories and empirical evidence. Findings The theories can be classified into individual-level theories explaining how women differ from men in terms of characteristics and behavior, and group-level theories explaining potential consequences of group diversity, not specifically gender diversity. The identified workplace outcomes include structural characteristics, internal functioning, organizational orientation and performance (incl. financial performance), with gender diversity mainly having a positive or no association. The complexity of sport in terms of types of sport organizations (for-profit, non-profit, public) and workers (volunteers, paid staff) was not considered theory-wise; only some outcomes were sport-specific. Research limitations/implications Since studies mostly applied psychological theories from the corporate literature to sport, future research may consider the peculiarities of the sport sector (e.g. non-profit organizations, volunteers) to a greater extent. Greater consideration could also be given to the collection of longitudinal data that allow identifying causes and effects as well as changes over time and to studying gender diversity in sport leadership from an intersectional lens. Originality/value This article is the first to integrate sport literature related to outcomes (as opposed to antecedents) of gender diversity in sport leadership.

Glaucoma-related vision loss is associated with stress, anxiety, and reduced quality of life. Because availability of psychological support and evidence-based life style information for patients are limited, we developed “VisionWise” (ViWi), a personalised digital lifestyle education course for glaucoma patients. We hypothesized that ViWi participation could improve subjective well-being, increase knowledge about the disease, increase positive lifestyle habits and possibly improve subjective vision. In this exploratory AB/BA study (N = 27), patients of the AB group participated in a nine-week ViWi course (A) followed by a waiting period (B) while the BA group waited before taking the course. All were asked to complete questionnaires on stress (PSQ-20), depression (PHQ-8), anxiety (GAD-7), subjective vision (NEI-VFQ-25), personality (NEO-FFI), and glaucoma-related knowledge at three time points. Intervention effects were analysed as pre-post comparison: AB:T1–T2 and BA:T1–T3. Subjective general vision improved significantly in group AB (p < .001) but also - unexpectedly - in group BA (p < .001) already during the waiting period, suggesting a placebo or expectancy effect. Changes were observed regarding stress-related measures, depressive symptoms, and anxiety. Some personality dispositions (higher agreeableness) were associated with greater reductions in anxiety and depressive symptoms. Usability ratings of ViWi were high, and no adverse events were observed. ViWi is a feasible and personalised digital lifestyle coaching tool to partially restore subjective vision in glaucoma patients. It can be used at home and empowers patients to cope with vision loss through behavioural eye exercises, management of stress-related risk factors, and novel strategies to adapt to low vision. Although the observed vision improvements are in part explainable by a placebo effect, this finding indirectly supports the relevance of positive attitudes in helping patients better control anxiety and stress, which are known co-factors in glaucoma progression. ViWi also supports patients in becoming better informed and more proactive in their glaucoma management. Our pilot study may guide future study designs to verify and optimise training effects through individualization, user engagement, and online accessibility as low-cost means “what else” they can do to complement standard glaucoma care. Within the framework of predictive, preventive and personalized medicine (PPPM), the present findings highlight the potential of digital lifestyle interventions to support patients´ awareness of psychosocial and stress-related risk factors, while exploratory analyses provide predictive insights into risk constellations associated with intervention outcomes. By addressing stress-related and behavioural factors, ViWi may contribute to a paradigm shift from reactive disease management towards a more personalised, positive, and patient-centred glaucoma care.

The anticandidal activity of Monotes kerstingii leaf and root crude extracts was evaluated against five clinical Candida isolates: C. albicans, C. parapsilosis, C. krusei, C. glabrata and C. tropicalis. Extracts from both organs displayed Minimal Inhibitory Concentrations (MICs) ranging from 3.9 to 2000µg/mL. Out of the five Candida species, the leaf hydroethanolic extract (EMKL) was the most active with MIC values of 3.9, 15.6 and 31.5µg/mL on C. krusei, C. parapsilosis and C. albicans, respectively. The chemical investigation of these extracts led to the characterization of six previously undescribed metabolites, including a glycosylated stilbene: kerstingioside (1), three cis stilbene-coumarins: cis-kerstilbcoumarin A-C (2-4) among which two as inseparable cis/trans-mixtures, one flavanone: kerstingiiflavanone (5) and one fatty acid glycoside, monestoside B (6), alongside with 22 known compounds. The distribution of the annotated metabolites in the roots and leaves was confirmed by comprehensive RP-UHPLC-Orbitrap-MS and MS/MS analysis. In addition, all the isolated compounds were screened for their anticandidal activity. Stilbene 7 was the most active constituent, with MICs of 7.8, 15.6, and 15.6µg/mL against C. albicans, C. krusei, and C. parapsilosis, respectively, while compounds 14 and 15 exhibited only moderate activity.

The Metaproteomics Initiative was officially launched in 2021 to strengthen collaboration, promote knowledge exchange, and support and lead standardization efforts within the growing metaproteomics community. Over the past five years, the Initiative has developed into a structured, global network of researchers. It has launched community-driven benchmark studies, helped shape emerging metadata and reporting standards, developed practical guidance and training materials, organized international symposia, and fostered connections across the microbiome research landscape (https://metaproteomics.org/). We outline the Initiative's organization, activities, achievements, and ongoing efforts, and reflect on how sustained, community-led coordination has shaped the development of metaproteomics as a field. We further position the Grand Metaproteome Challenges as a next step toward coordinated, community-scale biological research, aimed at advancing functional microbiome studies across clinical, industrial, and environmental application domains, and invite engagement from the wider microbiome and omics communities.

Purpose Asynchronous interactions pervade global teams, yet how time delays shape leadership remains underexplored. This study examines temporal distance – the delay between leader–follower interactions – as a boundary condition moderating leadership effectiveness in global virtual teams, developing a framework for asynchronous leadership adaptations. Design/methodology/approach An integrative review synthesized 82 multidisciplinary studies on virtual leadership and asynchronous team coordination, using multilevel categorization (micro, meso, macro) with systematic clustering of temporal mechanisms and boundary conditions. Findings Temporal distance systematically moderates leadership transmission: the effectiveness of task-oriented behaviors appears to remain robust under delay, whereas relationship-oriented behaviors weaken; temporal adaptability and virtual relationship quality buffer these losses. Research limitations/implications The framework’s primary focus is on globally distributed teams with significant time zone separation; applicability to hybrid or local asynchronous teams may be limited, suggesting need for future research extensions. Practical implications Beyond improving team coordination, the framework provides actionable insights for global organizational strategic management by enabling leaders to design temporally resilient structures that enhance collaboration, retention, and competitive agility in multinational contexts. Social implications Enhanced temporal leadership promotes inclusive global work environments by overcoming geographic and temporal barriers to participation and career growth. Originality/value Unlike previous research treating temporal aspects as secondary, this study positions temporal distance as a significant boundary condition requiring distinct leadership adaptations. The framework advances virtual leadership theory by explaining previously inconsistent findings and identifying mechanisms through which time separation moderates leadership processes.

Plant responses to leaf-mining insects are still poorly studied, especially in woody species. Robinia pseudoacacia is widely cultivated in Ukraine, where it is not native. There, the trees are facing increasing damage from the likewise introduced leaf miner species Parectopa robiniella and Macrosaccus robiniella. We examined the effects of infestation by these species on foliar carbon (C) and nitrogen (N) content and on metabolic fingerprints of trees of different age and at different locations, expecting context dependency in induction responses. Uninfested or miner-infested leaflets were collected from infested trees of three age classes at one location and from trees of one age class at four distinct locations. C and N content were mostly determined by location, with minor effects of tree age and herbivory, for N in interaction. Among the 3,121 metabolic features detected with UHPLC-QTOF-MS/MS, 1,087 were quantitatively modulated by herbivory in at least one age–location combination. Metabolic responses to the two leaf miner species partially overlapped. The magnitude and direction of metabolic shifts varied with both tree age and location. The differences in leaf biochemistry and in responses to herbivory between tree age classes and locations may reflect physiological constraints, past environmental conditions, age-dependent defense strategies, resource availabilities and allocation as well as local edaphic and microclimatic conditions, but potentially also different damage levels. That the leaflets of R. pseudoacacia exhibited context-dependent biochemical responses to the leaf miners highlights the importance of accounting for plant ontogenetic stage and local environmental heterogeneity when evaluating plant–leaf miner interactions.

Targeted therapies (TT) improve outcomes in BRAF-mutant melanoma. Pre-clinical data suggest that anticoagulation (AC) and platelet aggregation inhibition (PAI) may have antitumoral effects. We evaluated the impact of concomitant AC or PAI on outcomes in patients receiving TT. We analyzed 1296 patients with unresectable stage III-IV BRAF-mutant melanoma treated with BRAF plus MEK inhibitors (2016-2024) in the prospective multicenter ADOReg registry. Patients were categorized as receiving no antithrombotic therapy (ATT; n = 1125), PAI (n = 73; acetylsalicylic acid or clopidogrel), or AC (n = 98; direct oral anticoagulants, low-molecular-weight heparin, or vitamin K antagonists). Median follow-up was 1.3 years. Compared with patients without ATT, those receiving AC had significantly improved 12-month progression-free survival (PFS; HR 0.55, 95 % CI 0.39-0.78, p = 0.001) and overall survival (OS; HR 0.35, 95 % CI 0.19-0.64, p = 0.001). Direct oral anticoagulants showed the most pronounced PFS benefit (HR 0.40, 95 % CI 0.25-0.64, p < 0.001). PAI was not associated with a significant difference in PFS, but multivariable Cox regression indicated a reduced hazard of death (HR 0.48, 95 % CI 0.27-0.87, p = 0.015). Concomitant AC, particularly factor Xa-inhibiting direct oral anticoagulants, was associated with improved survival in melanoma patients undergoing TT. These findings support prospective trials evaluating AC as concomitant therapy in advanced melanoma.