Tackling tumour cell heterogeneity at the super-resolution level in human colorectal cancer tissue

Tumour cell heterogeneity, and its early individual diagnosis, is one of the most fundamental problems in cancer diagnosis and therapy. Single molecule localisation microscopy (SMLM) resolves subcellular features but has been limited to cultured cell lines only. Since nuclear chromatin architecture and microRNAs are critical in metastasis, we introduce a first-in-field approach for quantitative SMLM-analysis of chromatin nanostructure in individual cells in resected, routine-pathology colorectal carcinoma (CRC) patient tissue sections. Chromatin density profiles proved to differ for cells in normal and carcinoma colorectal tissues. In tumour sections, nuclear size and chromatin compaction percentages were significantly different in carcinoma versus normal epithelial and other cells of colorectal tissue. SMLM analysis in nuclei from normal colorectal tissue revealed abrupt changes in chromatin density profiles at the nanoscale, features not detected by conventional widefield microscopy. SMLM for microRNAs relevant for metastasis was achieved in colorectal cancer tissue at the nuclear level. Super-resolution microscopy with quantitative image evaluation algorithms provide powerful tools to analyse chromatin nanostructure and microRNAs of individual cells from normal and tumour tissue at the nanoscale. Our new perspectives improve the differential diagnosis of normal and (metastatically relevant) tumour cells at the single-cell level within the heterogeneity of primary tumours of patients

Design and application of an algorithm for analysis of a relationship between DNA damage and replication

Skonstruowano algorytm do ilościowej analizy relacji przestrzennych między dyskretnymi (punktowymi) zdarzeniami w komórkach.. Zastosowano go do analizy zależności pomiędzy sygnalizacją uszkodzenia DNA (fosforylacja histonu H2AX) ,a replikacją DNA w jądrach komórek traktowanych kamptotecyną lub nadtlenkiem wodoru. Relacje przestrzenne pomiędzy dwoma zdarzeniami były wyznaczane według zasady "najbliższy sąsiad". W komórkach traktowanych kamptotecyną (inhibitor topoizomerazy typu I) uszkodzenia indukowane są preferencyjnie w obszarach replikacji, natomiast nadtlenek wodoru wywołuje uszkodzenia zarówno w miejscach replikacji, jak i po za nimi. Blokowanie widełek replikacyjnych wywołane przez kamptotecynę lub nadtlenek wodoru może prowadzić do aktywacji nowych miejsc replikacji.An algorithm for quantitative analysis of spatial relationships between discrete events (foci) in cells was constructed and applied in analysis of a relationship between DNA damage signaling (H2AX histone phosphorylation), and DNA replication in nuclei of cells treated with camptothecin or hydrogen peroxide. Spatial relations between the two events were determined using the "nearest neighbor" approach. Camptothecin (topoisomerase I inhibitor) induced damage primarily in areas of DNA replication, while hydrogen peroxide caused DNA damage in replicating as well as nonreplicating DNA. Blocking replication forks by camptothecin or hydrogen peroxide may lead to activation of new replication foci

Accelerated wound closure rate by hyaluronic acid release from coated PHBV electrospun fiber scaffolds

The enormous potential of electrospun polymer fibers allows for their development in the field of biomaterials for tissue engineering and wound healing. Electrospun fibers based on biodegradable polymers such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are an ideal material for the production of a biocompatible cell scaffold supporting wound closure and skin regeneration. The aim of this research was to create a fibrous PHBV scaffold supporting the 3D environment for anchoring and proliferation of keratinocytes. Moreover, hyaluronic acid (HA) has been used as a coating on PHBV fibers to improve the wound closure processes. ATR-FTIR results indicated the presence of HA in the PHBV scaffolds and UV-Vis analysis confirmed the release of HA from the fibers over 24h test. Importantly, this release of HA increase keratinocyte activity as well their proliferation leading to accelerated wound closure rate in the scratch tests. The designed HA-coated PHBV scaffolds demonstrate the great potential of surface-modified electrospun polymer fibers for wound healing

Business Process Management education in Poland: A manifesto for academic teaching

This paper critically assesses Business Process Management (BPM) education in Poland and provides evidence-based recommendations for improvement. Through a survey of 44 BPM educators, the study evaluates BPM lifecycle coverage, IT tool utilization, and incorporation of the Six Core Elements of BPM. The findings reveal a focus on process modeling and analysis, identifying gaps in the way the entire BPM lifecycle is addressed. Despite the utilization of various IT tools, there is a notable absence of coverage for emerging topics such as process mining, AI, and Robotic Process Automation. Only 12% of courses cover all Six Core Elements of BPM, and there is a critical gap in student education, which is the underrepresentation of the People and Culture elements. The paper concludes with a manifesto for greater alignment between academic education and industry needs through comprehensive BPM curricula, dedicated software tools, and more robust coverage of the strategic and governance aspects of BPM. This will bridge the gap between academic education and real-world BPM applications, so that graduates can be better prepared for the challenges of the modern business landscape, which can enhance the quality and effectiveness of BPM education, thereby aligning it with the evolving demands of the business environment and contributing to the growth and competitiveness of organizations in Poland