Fanconi anemia (FA) is a rare disease (incidence of 1:300,000) primarily based on the inheritance of pathogenic variants in genes of the FA/BRCA (breast cancer) pathway. These variants ultimately reduce the functionality of different proteins involved in the repair of DNA interstrand crosslinks and DNA double-strand breaks. At birth, individuals with FA might present with typical malformations, particularly radial axis and renal malformations, as well as other physical abnormalities like skin pigmentation anomalies. During the first decade of life, FA mostly causes bone marrow failure due to reduced capacity and loss of the hematopoietic stem and progenitor cells. This often makes hematopoietic stem cell transplantation necessary, but this therapy increases the already intrinsic risk of developing squamous cell carcinoma (SCC) in early adult age. Due to the underlying genetic defect in FA, classical chemo-radiation-based treatment protocols cannot be applied. Therefore, detecting and treating the multi-step tumorigenesis process of SCC in an early stage, or even its progenitors, is the best option for prolonging the life of adult FA individuals. However, the small number of FA individuals makes classical evidence-based medicine approaches based on results from randomized clinical trials impossible. As an alternative, we introduce here the concept of multi-level dynamical modelling using large, longitudinally collected genome, proteome- and transcriptome-wide data sets from a small number of FA individuals. This mechanistic modelling approach is based on the "hallmarks of cancer in FA", which we derive from our unique database of the clinical history of over 750 FA individuals. Multi-omic data from healthy and diseased tissue samples of FA individuals are to be used for training constituent models of a multi-level tumorigenesis model, which will then be used to make experimentally testable predictions. In this way, mechanistic models facilitate not only a descriptive but also a functional understanding of SCC in FA. This approach will provide the basis for detecting signatures of SCCs at early stages and their precursors so they can be efficiently treated or even prevented, leading to a better prognosis and quality of life for the FA individual.
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http://dx.doi.org/10.3389/fgene.2023.1254966 | DOI Listing |
Nanomaterials (Basel)
December 2024
Department of IT & Semiconductor Convergence Engineering, Tech University of Korea, Siheung 15073, Republic of Korea.
This study presents the fabrication and characterization of a dual-functional Pt/GaO/Pt optoelectronic synaptic device, capable of operating as both a memristor and a memcapacitor. We detail the optimized radio frequency (RF) sputtering parameters, including a base pressure of 8.7 × 10 Torr, RF power of 100 W, working pressure of 3 mTorr, and the use of high-purity GaO and Pt targets.
View Article and Find Full Text PDFFront Psychol
November 2024
Department of Psychology, Bursa Uludağ University, Bursa, Türkiye.
Research on flashbulb memories (FBMs) has primarily focused on cognitive aspects. However, recent studies indicate that FBMs are closely associated with social and cultural dynamics. This descriptive study explored the structural aspects and psychosocial functions of negative FBMs within the context of intergroup theories, mainly focusing on negative public (coup attempt in Türkiye on July 15, 2016) and private (bad news of a loved one) FBMs.
View Article and Find Full Text PDFJ Hazard Mater
December 2024
Institute of Translational Pharmacology (IFT), National Research Council (CNR), Via Ugo La Malfa 153, Palermo 90146, Italy. Electronic address:
The innate immune system is the first player involved in the recognition/interaction with nanomaterials. Still, it is not the only system involved. The co-evolution of the microbiota with the innate immune system built an interdependence regulating immune homeostasis that is poorly studied.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544-5263, USA.
Solutions and minerals containing sulfate (SO42-), and Ca2+ and Mg2+ cations, are ubiquitous throughout the lithosphere and are significant components of seawater, thus presenting a prototypical system for the study of strong electrolytes and crystal nucleation mechanisms. However, despite their relative abundance, key questions remain unanswered about the most fundamental atomic-level steps of their mineralization pathways and aqueous dynamics. Here, we carry out enhanced sampling multi-level molecular dynamics (MD) embedded correlated wavefunction theory simulations to elucidate ion-pairing mechanisms for Mg-SO4 and Ca-SO4 in concentrated aqueous solution, accurately capturing effects arising from both structural dynamics and electron exchange-correlation.
View Article and Find Full Text PDFPeerJ Comput Sci
December 2024
Dipartimento di Elettronica, Informazione e Bioingeneria, Politecnico di Milano, Milan, Italy.
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