Purpose: Immune checkpoint inhibition (ICI) shows benefits in adjuvant (AT) and neoadjuvant melanoma treatments. However, ICI frequently induces severe immune-related adverse events (irAE). Unlike metastatic disease, in which irAEs are a clinical trade-off for treatment that improves survival, the toxicity burden from ICI in the AT setting is a substantial clinical problem urging for irAE-predictive biomarkers.
View Article and Find Full Text PDFPostepy Kardiol Interwencyjnej
December 2023
Introduction: A substantial proportion of patients with chronic coronary syndromes suffer from angina even after medical treatment and revascularization. Coronary microvascular dysfunction (CMD) is discussed as a potential mechanism.
Aim: To assess angina status in patients with chronic coronary syndromes undergoing functional assessment of coronary circulation regarding the presence of coronary microcirculatory dysfunction.
Gene transcription by RNA polymerase II (Pol II) is under control of promoters and distal regulatory elements known as enhancers. Enhancers are themselves transcribed by Pol II correlating with their activity. How enhancer transcription is regulated and coordinated with transcription at target genes has remained unclear.
View Article and Find Full Text PDFCellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) comprising transcription factors (TFs) and the effectors of cytokine signaling. Based largely on analyses conducted at steady state, these GRNs are thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation.
View Article and Find Full Text PDFDiverse cellular phenotypes are determined by groups of transcription factors (TFs) and other regulators that influence each others' gene expression, forming transcriptional gene regulatory networks (GRNs). In many biological contexts, especially in development and associated diseases, the expression of the genes in GRNs is not static but evolves in time. Modeling the dynamics of GRN state is an important approach for understanding diverse cellular phenomena such as cell-fate specification, pluripotency and cell-fate reprogramming, oncogenesis, and tissue regeneration.
View Article and Find Full Text PDFSmall non-coding RNAs (sncRNAs) play important roles in health and disease. Next Generation Sequencing (NGS) technologies are considered as the most powerful and versatile methodologies to explore small RNA (sRNA) transcriptomes in diverse experimental and clinical studies. Small RNA-Seq (sRNA-Seq) data analysis proved to be challenging due to non-unique genomic origin, short length, and abundant post-transcriptional modifications of sRNA species.
View Article and Find Full Text PDFG3 (Bethesda)
December 2019
Cell-fate decisions during development are controlled by densely interconnected gene regulatory networks (GRNs) consisting of many genes. Inferring and predictively modeling these GRNs is crucial for understanding development and other physiological processes. Gene circuits, coupled differential equations that represent gene product synthesis with a switch-like function, provide a biologically realistic framework for modeling the time evolution of gene expression.
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