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The effect of the large cation matrix and delocalization of electronic density on the switchable behaviour of heterotrimetallic cyanido-bridged clusters
No full textStudies of the motifs that regulate subcellular localization reveal differences between the homologous neuronal proteins NeuroD1 and NeuroD2
No full textBackground: NeuroD1 and NeuroD2, members of the bHLH transcription factors family, are key regulators of nervous system development and function. While they share similar roles in neuronal regulation, their divergent expression patterns and specialized functions suggest the complexity of transcriptional control they perform. The activity of bHLH TFs depends on tightly regulated intracellular trafficking orchestrated by NLSs and/or NESs located within the protein’s sequences. A detailed characterization of these molecular motifs is essential to understand the mechanisms regulating NeuroD1 and NeuroD2 functions. Methods:
We prepared cDNA vector that enabled expression of the full-length and truncated variants of NeuroD1 and NeuroD2 fused to YFP in COS-7 and N2a cells. Confocal microscopy was used to assess intracellular localization and to identify the location of motifs presenting NLS, NES, and NoLS activity. Results: We demonstrated that previously documented NLS (NLS1), conserved both in NeuroD1 and NeuroD2 also presents NoLS (NoLS1) activity, revealing unexpected dual functionality. Additionally, we identified overlapping NLS2 and NES1 within the bHLH domains of both proteins. Notably, NeuroD2 harbours distinct NLS3 and a second NoLS (NoLS2) motifs, located in the C-terminal region. These elements, suggest differentiated regulation and specialization between the homologs. Conclusions: Our study reveals a surprisingly complex network of overlapping localization signals in NeuroD1 and NeuroD2 that regulate their cyto-nuclear trafficking. The presence of multiple, potentially competing signals suggests that their activity may be fine-tuned by specific ligands or interacting partners, adding further complexity to their regulation. These findings provide novel insight into how subcellular localization contributes to the functional divergence of homologous transcription factors
Sequential deposition enables suppression of spontaneous donor enrichment of the surface in spin-coated films
No full textSequential deposition (SD) through independent processing of donor and acceptor materials, has emerged as a promising strategy to enable better control over the active layer morphology of organic solar cells. In this work, time-of-flight secondary ion mass spectrometry was employed to investigate the vertical distribution of SD PM6/Y5 films and bulk heterojunction PM6:Y5 films coated from a blend solution in one-step process. The influence of thermal annealing (TA) on the vertical distribution of the components was also evaluated. Our results show that SD inverts the vertical distribution within the active layer, while TA helps to suppress Y5 diffusion into the PM6 layer. Additionally, near edge x-ray absorption fine structure spectroscopy (NEXAFS) was used to investigate the molecular orientation of the donor PM6 and the acceptor Y5, in SD and blend films. Depth-dependent molecular orientation was assessed by comparing NEXAFS spectra acquired in total electron yield and fluorescence yield. Nitrogen K-edge NEXAFS spectra were employed to selectively probe the acceptor orientation. In SD-processed samples, we found that Y5 retains its face-on orientation when deposited on top of PM6, despite the combined effects of film formation dynamics and interfacial intermixing inherent to the process
Global education and training in geriatrics : mapping transnational initiatives and their complementarities
No full textEmigration : the records of fate
No full textKim jest pisarz na obczyźnie? Co spełni się w jego losie? Czym jest życie zapisane w mowie ojczyzny, którą się opuściło? I czym dla pisarza na obczyźnie jest ojczyzna mowy, w której uprawia literaturę? Eseje Wojciecha Ligęzy krążą wokół kwestii wywiedzionych z pisarstwa polskich emigrantów XX wieku. Są kompetentne, przenikliwe w odczytaniach, intrygujące. Uprawiana w nich antropologia emigracji to namysł nad przeplotami obcości i zadomowienia, wolności życia w drodze i przekleństwa bycia przybyszem, twórczej swobody i konieczności nieustannego zaczynania od nowa, prozy materializujących się mitów i przebłysków transcendencji, kręgów wygnania i ścieżek powrotu
Charitable potential of sports journalism on the Internet : modeling communication about charitable actions by athletes, sports journalists and non-profit organizations
No full text
No full textAdeno-associated virus (AAV) vectors have become a cornerstone of in vivo gene delivery. However, although the endothelium is the first cellular interface encountered after systemic delivery, native AAV serotypes exhibit poor endothelial transduction, favoring hepatocytes, muscle cells and, neurons instead. This limitation represents a major barrier to gene therapies targeting cardiovascular, neurovascular, and inflammatory diseases. This review summarizes recent advances in redirecting AAV tropism toward endothelial cells (ECs) through genetic capsid engineering, peptide display, and non-genetic surface modification. We highlight the previously underrecognized endothelial tropism of the AAV4 serotype, attributed to its unique recognition of O-linked sialic acids. We also describe multiple approaches to capsid retargeting, including the incorporation of EC-binding peptides that enable cell entry into specific vascular beds, as well as genetic engineering strategies that reduce heparan sulfate proteoglycan (HSPG) binding and hepatocyte transduction while enhancing intracellular trafficking in ECs. In addition, we discuss polymer-coating approaches that allow receptor-specific targeting of ECs with reduced recognition by immune cells. Together, these strategies represent promising avenues for enhancing vascular tropism and transduction efficiency of modified AAVs, moving the field closer to precise vascular gene therapies
ToF-SIMS reveals metformin-driven restoration of hepatic lipid and amino acid profiles in a type 2 diabetes rat model
No full textDiabetes mellitus profoundly disturbs hepatic metabolism by impairing lipid and amino acid homeostasis, yet spatially resolved molecular evidence of these alterations remains limited. This study employed Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to visualise and quantify metabolic remodelling in rat liver under diabetic conditions and following metformin treatment. Liver cryosections from lean controls (LEAN), diabetic rats (P1), and metformin-treated diabetic rats (P2) were analysed in the negative ion mode, and all spectra were normalised to total ion counts. One-way ANOVA with false discovery rate (FDR) correction identified 43 lipid-related and 20 amino acid-related ions with significant group differences. Diabetic livers exhibited a marked depletion of phospholipid- and fatty acid-related ions (e.g., m/z 241.04, 281.25, 536.38) accompanied by increased ceramide fragments (m/z 805–806), indicating lipotoxic remodelling and mitochondrial stress. Simultaneously, aromatic and neutral amino acids such as phenylalanine, tyrosine, and glutamine were reduced, while small acidic fragments were elevated, consistent with enhanced proteolysis and gluconeogenic flux. Metformin administration partially restored both lipid and amino acid profiles toward the control phenotype. Hierarchical clustering and spatial ion maps revealed distinct group separation and partial normalisation of hepatic molecular patterns. These results demonstrate that ToF-SIMS provides label-free, spatially resolved insights into diabetes-induced metabolic disturbances and metformin-driven hepatoprotection
