Search Results (84,250)

A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin’s origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants. Full article

Background: Pulmonary vein isolation (PVI) is the standard of care for the treatment of symptomatic atrial fibrillation (AF). Novel techniques for PVI are the thermal size-adjustable cryo-balloon (CB) system and non-thermal pulsed field ablation (PFA) system. There are currently no data available for a direct comparison between these two systems. Furthermore, with new techniques, it is important to ensure a high level of efficiency and safety during treatment right from initial use. Therefore, the aim of this study was to directly compare the procedural data and safety of these two new PVI techniques in first-time users. Methods: We conducted a single-center prospective study involving 100 consecutive patients with symptomatic atrial fibrillation who underwent first-time PVI using either size-adjustable CB PVI or PFA PVI from July 2023 to March 2024. Results: Acute PVI was achieved in 100% of patients in both groups. First-pass isolation (FPI) was more frequently achieved in the PFA group compared to the size-adjustable CB group. The mean procedural duration and fluoroscopy dose were significantly shorter in the PFA cohort (p < 0.001). Furthermore, a significant reduction in fluoroscopy time was observed during the learning curve within the PFA group (p = 0.023). There were no major complications in both groups. Conclusions: Both systems demonstrate good effectiveness and safety during PVI performed by first-time users. However, the PFA group exhibited a significantly shorter procedural duration. Full article

The climate-driven challenges facing Earth necessitate a comprehensive understanding of the mechanisms facilitating plant resilience to environmental stressors. This review delves into the crucial role of ubiquitin-like modifiers, particularly focusing on ATG8-mediated autophagy, in bolstering plant tolerance to salt stress. Synthesising recent research, we unveil the multifaceted contributions of ATG8 to plant adaptation mechanisms amidst salt stress conditions, including stomatal regulation, photosynthetic efficiency, osmotic adjustment, and antioxidant defence. Furthermore, we elucidate the interconnectedness of autophagy with key phytohormone signalling pathways, advocating for further exploration into their molecular mechanisms. Our findings underscore the significance of understanding molecular mechanisms underlying ubiquitin-based protein degradation systems and autophagy in salt stress tolerance, offering valuable insights for designing innovative strategies to improve crop productivity and ensure global food security amidst increasing soil salinisation. By harnessing the potential of autophagy and other molecular mechanisms, we can foster sustainable agricultural practices and develop stress-tolerant crops resilient to salt stress. Full article

The opacity of the impact investment decision-making process is one of the main constraints hampering further growth in the impact investing ecosystem. This paper takes a differentiated view on why (investment motivation) and how (investment decision criteria) the major private impact investor types allocate funding to investees. We incorporate insights from 34 interviews with the five major impact investor types: social business angels, foundations, social banks, impact investment funds, and crowdvesting platforms. We find that motivation and decision-making significantly differ between the impact investor types, especially concerning strict vs. ambiguous impact definitions, active vs. passive investment approaches, and return requirements reaching from capital preservation to market-driven returns. By providing a differentiated overview of the investor type-specific motivations and most important investment criteria, our study offers social entrepreneurs a roadmap to identify the most appropriate impact investors for their business model. Full article

Since there is a broad empirical consensus that linear science communication focusing on disaster framing rarely empowers audiences and prompts transformative action, alternative climate communication formats are needed. This paper explores an alternative climate communication format, which integrates the issue into a local context (Munich, Germany) via transdisciplinary cooperation, specifically through collaboration with local climate educators and tapping into the scientific expertise of local stakeholders. The conceptualized format of a City Walk on the subject of climate justice addresses urban citizens and tests the effectiveness of climate justice as an alternative framing. Drawing on an accompanying empirical study with qualitative group discussions (n = 14, October 2023), this article explores how the format and framing are perceived by the participants. Based on these findings, we discuss the potentials and pitfalls of the format for transdisciplinary science communication. In summary, the City Walk deepened participants’ understanding of local climate justice—that is to say, how heat and flooding could amplify existing inequalities, and why adaptation and mitigation measures have not yet been implemented more thoroughly. Here, the crucial point is not whether the shift from climate change being a general topic to a personal one is supported by technical aspects of communication (e.g., virtual simulations). However, perceived local climate justice barriers (like bureaucracy) led participants to prioritize individual action (‘footprint’) over collective action (e.g., addressing local change). With these results, this study underlines the importance of new transdisciplinary formats for climate communication to address local change. Full article

The post-harvest processing of coffee beans leads to a wide range of reactions involving proteins. The formation of crosslinks between proteins and phenolic compounds present in high concentrations of coffee beans represents one of the most challenging and still not fully characterized reactions. The aim of this work was to assess the presence of products from such reactions in coffee samples, focusing on the adducts between cysteine and chlorogenic acids (CQAs). For this purpose, 19 green and 15 roasted coffee samples of the Coffea arabica, Coffea canephora, and Coffea liberica varieties were selected for this study and basically characterized. Then, targeted liquid chromatography mass spectrometry (LC-MS/MS) methods were developed to assess the formation of adducts between CQA and cysteine, glutathione, and N-acetylcysteine as the amino acid and peptide models, and quantified such adducts in coffee samples. The results of the characterization showed a heterogeneous distribution of the protein content (8.7–14.6%), caffeine (0.57–2.62 g/100 g), and antioxidant capacity (2–4.5 g ascorbic acid/100 g) in Arabica, Canephora, and Liberica samples. Glutamic acid, arginine, and proline were found to be the major amino acids, while 5-CQA (38–76%), 3-CQA (4–13%), and 4-CQA (4–13%) were the most abundant CQA derivatives of all coffee varieties. The model experiments for adduct formation demonstrated that cysteine binds to CQA via thiol groups and 5-CQA initially isomerizes to 3- and 4-CQA, depending on the conditions, allowing cysteine to bind to two different sites on 3-, 4- or 5-CQA molecules, thus, forming six different Cys-CQA adducts with m/z 476. The reaction was more favored at pH 9, and the adducts proved to be stable up to 90 °C for 10 min and up to 28 days at room temperature. The relative quantification of adducts showed peak area values ranging from 1100 to 3000 in green coffee bean samples, while no adducts were detected in roasted coffee beans. Overall, this work was the first attempt to demonstrate the presence of Cys-CQA adducts in coffee beans and paves the way for further investigations of such adduct formation at the protein level. Full article

In this work, a new plastic-intensive medium-pressure plate (MPP), which is part of a fuel-cell system, has been developed together with a steel plate meeting all mechanical and chemical requirements. This newly developed MPP had to achieve the objective of saving weight and package space. The use of compression molding as a manufacturing technique facilitated the use of glass mat thermoplastics (GMT) which has higher E-modules and strength compared to most of the injection molded materials. A steel plate was placed as an insert to help achieve the stiffness requirements. For the development, the existing MPP was benchmarked for its structural capabilities and its underlying functional features. Four different FRP materials were investigated in terms of their chemical and mechanical properties. PP-GMT material, which has both high mechanical performance and resistance against chemicals in the fuel cell fluid, had been chosen. Using the properties of the chosen PP-GMT material, topology optimization was carried out based on the quasi-static load case and manufacturing constraints, which gave a load-conforming rib structure. The obtained rib structure was utilized to develop the final MPP with adherence to the functional requirements of MPP. The developed plastic-intensive MPP exhibits a 3-in-1 component feature with a 55% reduction in package space and an 8% weight reduction. The MPP was virtually analyzed for its mechanical strength and compared with the existing benchmark values. Finally, a press tool was conceptualized and manufactured to fabricate the new plastic-intensive MPP, which was tested in a rig and validated in the FE model. Full article

We previously demonstrated that diet supplementation with seaweed Sargassum fusiforme (S. fusiforme) prevented AD-related pathology in a mouse model of Alzheimer’s Disease (AD). Here, we tested a lipid extract of seaweed Himanthalia elongata (H. elongata) and a supercritical fluid (SCF) extract of S. fusiforme that is free of excess inorganic arsenic. Diet supplementation with H. elongata extract prevented cognitive deterioration in APPswePS1ΔE9 mice. Similar trends were observed for the S. fusiforme SCF extract. The cerebral amyloid-β plaque load remained unaffected. However, IHC analysis revealed that both extracts lowered glial markers in the brains of APPswePS1ΔE9 mice. While cerebellar cholesterol concentrations remained unaffected, both extracts increased desmosterol, an endogenous LXR agonist with anti-inflammatory properties. Both extracts increased cholesterol efflux, and particularly, H. elongata extract decreased the production of pro-inflammatory cytokines in LPS-stimulated THP-1-derived macrophages. Additionally, our findings suggest a reduction of AD-associated phosphorylated tau and promotion of early oligodendrocyte differentiation by H. elongata. RNA sequencing on the hippocampus of one-week-treated APPswePS1ΔE9 mice revealed effects of H. elongata on, amongst others, acetylcholine and synaptogenesis signaling pathways. In conclusion, extracts of H. elongata and S. fusiforme show potential to reduce AD-related pathology in APPswePS1ΔE9 mice. Increasing desmosterol concentrations may contribute to these effects by dampening neuroinflammation. Full article

Cow uterine infections pose a challenge in dairy farming, resulting in reproductive disorders. Uterine fluid extracellular vesicles (UF-EVs) play a key role in cell-to-cell communication in the uterus, potentially holding the signs of aetiology for endometritis. We used mass spectrometry-based quantitative shotgun proteomics to compare UF-EV proteomic profiles in healthy cows (H), cows with subclinical (SE) or clinical endometritis (CLE) sampled at 28–35 days postpartum. Functional analysis was performed on embryo cultures with the exposure to different EV types. A total of 248 UF-EV proteins exhibited differential enrichment between the groups. Interestingly, in SE, EV protein signature suggests a slight suppression of inflammatory response compared to CLE-UF-EVs, clustering closer with healthy cows’ profile. Furthermore, CLE-UF-EVs proteomic profile highlighted pathways associated with cell apoptosis and active inflammation aimed at pathogen elimination. In SE-UF-EVs, the regulation of normal physiological status was aberrant, showing cell damage and endometrial repair at the same time. Serine peptidase HtrA1 (HTRA1) emerged as a potential biomarker for SE. Supplementation of CLE- and SE-derived UF-EVs reduced the embryo developmental rates and quality. Therefore, further research is warranted to elucidate the precise aetiology of SE in cattle, and HTRA1 should be further explored as a potential diagnostic biomarker. Full article

Cysteine cathepsins F and W are members of the papain-like cysteine protease family, which have distinct structural features and functional roles in various physiological and pathological processes. This review provides a comprehensive overview of the current understanding of the structure, biological functions, and pathological implications of cathepsins F and W. Beginning with an introduction to these proteases, we delve into their structural characteristics and elucidate their unique features that dictate their enzymatic activities and substrate specificity. We also explore the intricate involvement of cathepsins F and W in malignancies, highlighting their role as potential biomarkers and therapeutic targets in cancer progression. Furthermore, we discuss the emerging roles of these enzymes in immune response modulation and neurological disorders, shedding light on their implications in autoimmune and neurodegenerative diseases. Finally, we review the landscape of inhibitors targeting these proteases, highlighting their therapeutic potential and challenges in clinical translation. This review brings together the diverse facets of cysteine cathepsins F and W, providing insights into their roles in health and disease and guiding future investigations for therapeutic advances. Full article

To date, there are almost no investigations addressing functional connectivity (FC) in patients with brain metastases (BM). In this retrospective study, we investigate the influence of BM on hemodynamic brain signals derived from functional magnetic resonance imaging (fMRI) and FC. Motor-fMRI data of 29 patients with BM and 29 matched healthy controls were analyzed to assess percent signal changes (PSC) in the ROIs motor cortex, premotor cortex, and supplementary motor cortex and FC in the sensorimotor, default mode, and salience networks using Statistical Parametric Mapping (SPM12) and marsbar and CONN toolboxes. In the PSC analysis, an attenuation of the BOLD signal in the metastases-affected hemisphere compared to the contralateral hemisphere was significant only in the supplementary motor cortex during hand movement. In the FC analysis, we found alterations in patients’ FC compared to controls in all examined networks, also in the hemisphere contralateral to the metastasis. This indicates a qualitative attenuation of the BOLD signal in the affected hemisphere and also that FC is altered by the presence of BM, similarly to what is known for primary brain tumors. This transformation is not only visible in the infiltrated hemisphere, but also in the contralateral one, suggesting an influence of BM beyond local damage. Full article

This study explores anxiety and depression among young individuals in Kosovo, considering socio-political and economic influences. Introducing Positive Youth Development (PYD) as a framework, the study explores its integration with Internal Cohesion Psychotherapy (ICP) to address youth mental health challenges. Empirical evidence underscores ICP’s positive impact on mental health outcomes, emphasizing developmental assets. Thematic analysis of participant narratives reveals six key themes, showcasing ICP’s transformative nature, the critical role of social support networks, values and beliefs, reflections on personal growth, and therapy’s extended impact on relationships. Participants’ stories highlight ICP’s profound influence on personal growth, social relationships, and mental health. The study examines internal and external assets, emphasizing social networks, values, beliefs, and cultural competence. Insights into ICP’s intrapersonal and professional systems reveal developmental assets fostering growth, motivation, and engagement. External assets like empowerment, safety, and service to others, alongside internal assets like commitment to learning, positive values, integrity, and responsibility, contribute to an understanding of factors influencing Kosovo’s young population. In conclusion, the integration of PYD and ICP offers a powerful synergy to address mental health challenges, providing valuable insights into specific developmental assets crucial for optimizing interventions and promoting mental health among young Kosovars. Full article

Due to the proliferation-induced high demand of cancer cells for folic acid (FA), significant overexpression of folate receptors 1 (FR1) is detected in most cancers. To our knowledge, a detailed characterization of FR1 expression and regulation regarding therapeutic and diagnostic feasibilities in prostate cancer (PCa) has not been described. In the present study, cell cultures, as well as tissue sections, were analyzed using Western blot, qRT-PCR and immunofluorescence. In addition, we utilized FA-functionalized lipoplexes to characterize the potential of FR1-targeted delivery into PCa cells. Interestingly, we detected a high level of FR1-mRNA in healthy prostate epithelial cells and healthy prostate tissue. However, we were able to show that PCa cells in vitro and PCa tissue showed a massively enhanced FR1 membrane localization where the receptor can finally gain its function. We were able to link these changes to the overexpression of GPI–transamidase (GPI-T) by image analysis. PCa cells in vitro and PCa tissue show the strongest overexpression of GPI-T and thereby induce FR1 membrane localization. Finally, we utilized FA-functionalized lipoplexes to selectively transfer pDNA into PCa cells and demonstrate the therapeutic potential of FR1. Thus, FR1 represents a very promising candidate for targeted therapeutic transfer pathways in PCa and in combination with GPI-T, may provide predictive imaging in addition to established diagnostics. Full article

Plants and algae use light not only for driving photosynthesis but also to sense environmental cues and to adjust their circadian clocks via photoreceptors. Aureochromes are blue-light-dependent photoreceptors that also function as transcription factors, possessing both a LOV and a bZIP domain. Aureochromes so far have only been detected in Stramenopile algae, which include the diatoms. Four paralogues of aureochromes have been identified in the pennate model diatom Phaeodactylum tricornutum: PtAureo1a, 1b, 1c, and 2. While it was shown recently that diatoms have a diel rhythm, the molecular mechanisms and components regulating it are still largely unknown. Diel gene expression analyses of wild-type P. tricornutum, a PtAureo1a knockout strain, and the respective PtAureo1 complemented line revealed that all four aureochromes have a different diel regulation and that PtAureo1a has a strong co-regulatory influence on its own transcription, as well as on that of other genes encoding different blue-light photoreceptors (CPF1, 2 and 4), proteins involved in photoprotection (Lhcx1), and specific bHLH transcription factors (RITMO1). Some of these genes completely lost their circadian expression in the PtAureo1a KO mutant. Our results suggest a major involvement of aureochromes in the molecular clock of diatoms. Full article

The optimal structural design is imperative in order to minimize material consumption and reduce the environmental impacts of construction. Given the complexity in the formulation of structural design problems, the process of optimization is commonly performed using artificial intelligence (AI) global optimization, such as the genetic algorithm (GA). However, the integration of AI-based optimization, together with visual programming (VP), in building information modeling (BIM) projects warrants further investigation. This study proposes a workflow by combining structure analysis, VP, BIM, and GA to optimize trusses. The methodology encompasses several steps, including the following: (i) generation of parametric trusses in Dynamo VP; (ii) performing finite element modeling (FEM) using Robot Structural Analysis (RSA); (iii) retrieving and evaluating the FEM results interchangeably between Dynamo and RSA; (iv) finding the best solution using GA; and (v) importing the optimized model into Revit, enabling the user to perform simulations and engineering analysis, such as life cycle assessment (LCA) and quantity surveying. This methodology provides a new interoperable framework with minimal interference with existing supply-chain processes, and it will be flexible to technology literacy and allow architectural, engineering and construction (AEC) professionals to employ VP, global optimization, and FEM in BIM-based projects by leveraging open-sourced software and tools, together with commonly used design software. The feasibility of the proposed workflow was tested on benchmark problems and compared with the open literature. The outcomes of this study offer insight into the opportunities and limitations of combining VP, GA, FEA, and BIM for structural optimization applications, particularly to enhance structural efficiency and sustainability in construction. Despite the success of this study in developing a workable, user-friendly, and interoperable framework for the utilization of VP, GA, FEM, and BIM for structural optimization, the results obtained could be improved by (i) increasing the callback function speed between Dynamo and RSA through specialized application programming interface (API); and (ii) fine-tuning the GA parameters or utilizing other advanced global optimization and supervised learning techniques for the optimization. Full article