43 research outputs found
Epigenetic and bioelectronic tools to study neural stem cells in health and disease
No full textBrain development is a highly controlled, complex, and dynamic process. The mechanisms of its control need to accommodate the constantly changing contexts which, overtime, support the emergence of new neural structures and functions. Epigenetic mechanisms, among others, underlie the various stages of neurodevelopment, while epigenetic dysregulation has been associated with neurodevelopmental disorders and cancer. The overall aim of this thesis was to employ epigenetic and bioelectronic tools, to study neural stem cells in health and disease, specifically in the context of brain cancer or as part of the therapeutic regimen in brain tumor treatment. This was achieved through four studies:In Paper I, we studied the global and specific effects of lithium on the gene expression and DNA methylation patterns of irradiated human neural stem and progenitor cells (hNSPCs). Here, we present that lithium, when administered after irradiation, induces changes in DNA methylation and gene expression in hNSPCs, potentially pointing to a shift from gliogenesis towards neurogenesis. Lithium and irradiation resulted in upregulation of the genes glutamate decarboxylase 2 (GAD2), gremlin1 (GREM1), ten eleven translocation methylcytosine dioxygenase 3 (TET3), and growth arrest and DNA damage inducible alpha (GADD45A), among others. These, taken together, point to lithium having a role in the epigenetic control of DNA methylation, in the context of irradiation, through TET3 and GADD45A, as well as promoting neurogenesis through GAD2 and also blocking gliogenesis through gremlin1-associated bone morphogenetic protein (BMP) signaling blockade.In Paper II, we studied whether irradiation and lithium promoted the growth of human high-grade glioma (hHGG) cells in 3D cultures. Two cell lines were used, SF8628 (histone 3 lysine 27, H3K27, mutant) and SF188 (histone 3 variant H3.3 wild type), which were 3D printed and treated with irradiation and lithium. Treatment with lithium did not point to any severe risk regarding cancer cell growth in hHGG cells.In Paper III, we investigated the use of a library of luminescent conjugated oligothiophenes (LCOs) as molecular probes for real-time NSPCs and glioblastoma-derived stem-like cell detection. In this study, we discovered that one probe, penta-hydrogen thiophene methylimidazole (p-HTMI), specifically stained live embryonic rodent brain- and human glioma-derived progenitors within 10 min of administration to the culture medium in vitro. For this reason, p-HTMI was named GlioStem. In Paper IV, we showed that GlioStem can be used to detect glioma stem cells, directly in glioblastoma tissue. The GlioStem-positive cells in glioblastoma biopsies were found to exhibit similar transcriptomic identity to oligodendrocyte progenitors and pro-neural stem cell subpopulations.Overall, the findings of the papers comprising this PhD thesis hold great promise to improve patient health and outcomes.List of scientific papersI. Irradiation and lithium treatment alter the global DNA methylation pattern and gene expression underlying a shift from gliogenesis towards neurogenesis in human neural progenitors. Neofytou, C.*, Backlund, A., Blomgren, K., Hermanson, O.*. Translational Psychiatry. 13, 258 (2023). *Corresponding authors. https://doi.org/10.1038/s41398-023-02560-w II. Effects of lithium and irradiation on 3D-printed human high-grade glioma cells. Dominguez Garcia, S., Neofytou, C., Hermanson, O.*. *Corresponding author. [Manuscript]III. Live Detection of Neural Progenitors and Glioblastoma Cells by an Oligothiophene Derivative. lkhanizadeh, S.#, Gracias, A.#, Åslund, A.K.O.#, Bäck, M.#, Simon, R., Kavanagh, E., Migliori, B., Neofytou, C., Nelander, S., Westermark, B., Uhrbom, L. ForsbergNilsson, K., Konradsson, P., Teixeira, A.I., Uhlén, P., Joseph, B., Hermanson, O.*, ∇, Nilsson, K.P.R.∇. ACS Applied Bio Materials. 6 (9), 3790–3797 (2023). #These authors contributed equally to this study. ∇These authors jointly directed this study. *Corresponding author. https://doi.org/10.1021/acsabm.3c00447 IV. Near-instant detection of glioma stem cells in live human glioblastoma tissue. Neofytou, C.#, Persson, O.#, Keane, L.#, Jensdottir, M., Joseph, B., Hermanson, O., lkhanizadeh, S.*. #These authors contributed equally to this study. *Corresponding author. [Manuscript]</p
Topology optimization for heat flow manipulation
No full textThe aim of this thesis is to explore the use of topology optimization in designing materials for heat flow manipulation. Specifically shielding, concentrating or even inverting the heat current was examined. The possibility to scale the problem from macro- to nano-dimensions by using topology optimization for nanoscale heat conduction was also investigated. An optimization tool for heat flux shielding, focusing and reversal is presented. Different objective functions were defined in order to shield, focus or reverse heat flow within an area surrounded by a composite material with anisotropic thermal conductivity. The composite material under consideration consisted of thermally conductive elliptical inclusions embedded in a poor conductive matrix. The effective thermal conductivity was defined based on the equivalent inclusion theory. The dependence of the anisotropic thermal conductivity on the angle that the inclusions make with the imposed gradient was then approximated via a coordinate transformation. The material distribution method for topology optimization was then used to find the optimum angle distribution of the inclusion angle for heat shielding, focusing and reversal. The use of topology optimization for heat conduction in nanostructures was also investigated. At such small length scales the classical Fourier model for heat conduction is no longer applicable. As the dimensions of a structure become comparable to the mean free path of heat carriers (electrons or phonons), heat transfer changes from diffusive to semi-ballistic. Length scale effects such as scattering of the heat carriers with other phonons, material interfaces and boundaries become important. To take into account all this length effects, a more accurate model is given by the kinetic theory. Specifically the Boltzmann Transport Equation (BTE) for phonon transport was used to model the transfer of heat. To solve the BTE, a deterministic discrete ordinates method (DOM) was used in combination with the finite element method. Using COMSOL Multiphysics, the Boltzmann transport equation was successfully coupled with the MMA optimization algorithm and a Helmholtz PDE based filter. The method was implemented for the optimization of a simple system in order to illustrate its applicability.Mechanical, Maritime and Materials EngineeringMaterials Science and Engineerin
Isolated Jejunal Perforation Following Bicycle Handlebar Injury in Adults: A Case Report
No full textCopyright © 2013 Kyriakos Neofytou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The small intestine is the third in frequency intraperitoneal organ which is injured after blunt trauma of the abdomen. In most of the cases, this type of injuries is accompanied by other injuries, which make it more difficult to diagnose. Failure of diagnosis and delay in treating these injuries significantly increase the morbidity and mortality of these patients. Abdominal visceral injuries after flipping the handlebar of the bike are common in children. Such injuries can cause injury to both solid and hollow abdominal viscera. Unlike children, adults ’ abdominal visceral injuries after flipping the bike’s handlebar are extremely rare. A 25-year-old man was admitted to our department due to progressively abdominal pain after an accident with the handlebar of his bike. The subsequent CT scan after per os administration of contrast medium revealed the presence of free intraperitoneal contrast. It is a rare case of jejunal perforation after flipping the handlebar of the bicycle which was treated by partial removal of the injured part of jejunum and end-to-end anastomosis. To the best of our knowledge this is the first time we describe such an injury with this mechanism to an adult. 1
Study of the ontogenesis of the behaviour in sea bass Dicentrarchus labrax, (Linnaeus, 1758)
No full textThe study of behaviour and its ontogenesis can reveal the relationships between an animal and its environment and also can lead humans to better choices concerning the rearing conditions in order to ensure welfare for fish in captivity. The present study was focused in the comparative description of the ontogenesis of behaviour and feeding behaviour of European sea bass reared with two different techniques: intensive and mesocosm. The study of ontogenesis was conducted from the prelarval stages of sea bass to the stage of early juveniles (Chapter 2). Later on, during nursery phase, several acute stressors were applied in order to study their effect on the swimming activity and behaviour in general (Chapter 3). The rearing conditions of fish under captivity can be variable and the levels of these variables can on many occasions affect fish´s welfare. They may lead fish to negative situations and to adopt abnormal behavioural patterns. So, sea bass juveniles were subjected to a series of potentially stressful rearing conditions in order to study the effect of these conditions on the distribution of sea bass and on their behaviour in general. The working goal of the latter study was to evaluate the impact of these parameters on the welfare of sea bass during this ontogenetic stage in captivity (Chapter 4).Η μελέτη της συμπεριφοράς και η οντογένεση της μπορεί να αποκαλύψει τις σχέσεις μεταξύ του ζώου και του περιβάλλοντος του, και να κατευθύνει τον άνθρωπο στην επιλογή των καταλληλότερων συνθηκών διαβίωσης και εκτροφής προκειμένου να εξασφαλιστεί η ευζωία των «αιχμάλωτων» ψαριών. Η παρούσα μελέτη επικεντρώθηκε στην συγκριτική περιγραφή της οντογένεσης της συμπεριφοράς κολύμβησης και διατροφής του εκτρεφόμενου λαυρακιού υπό δύο διαφορετικές συνθήκες εκτροφής: εντατική μέθοδος και μέθοδος μεσοκόσμου. Η μελέτη της οντογένεσης πραγματοποιήθηκε από τα προνυμφικά στάδια του λαυρακιού μέχρι και την φάση των μεταμορφωμένων ιχθυδίων (γόνου: Κεφάλαιο 2). Στη συνέχεια, έγιναν διάφορες παρεμβάσεις στο περιβάλλον κολύμβησης των ιχθυδίων, στο στάδιο της προπάχυνσης (γόνου), προκειμένου να εκτιμηθεί η επίδραση τους στην κολύμβηση και γενικότερα στην συμπεριφορά τους. Οι παρεμβάσεις αυτές αφορούσαν σε αιφνίδιες (acute) αλλαγές μέσα στο μέσο κολύμβησης που πιθανόν να λειτουργούσαν ως διαταραχές (Κεφάλαιο 3). Οι συνθήκες διαβίωσης των ψαριών στην αιχμαλωσία είναι μεταβλητές και οι τιμές αυτών των μεταβλητών μπορεί να επηρεάσουν σε πολλές περιπτώσεις την ευζωία των ψαριών. Μπορεί να τα οδηγήσουν σε αρνητικές καταστάσεις και υιοθέτηση προτύπων μη φυσιολογικής συμπεριφοράς. Έτσι, ιχθύδια λαυρακιού υποβλήθηκαν σε μία σειρά στρεσογόνων συνθηκών διαβίωσης προκειμένου να διαπιστωθεί η επίδραση αυτών στην κατανομή τους στον χώρο αλλά και στην συμπεριφορά τους γενικότερα με απώτερο στόχο την εκτίμηση των παραμέτρων αυτών ως προς την ευζωία του λαυρακιού στο αναπτυξιακό αυτό στάδιο κατά την αιχμαλωσία του (Κεφάλαιο 4)
Predicting fetoplacental chromosomal mosaicism during non-invasive prenatal testing
No full textNon-invasive prenatal detection of aneuploidies can be achieved with high accuracy through sequencing of cfDNA in the maternal blood plasma. However, false positive and negative NIPT results remain. Fetoplacental mosaicism is the main cause for false positive and false negative NIPT. We set out to develop a method to detect placental chromosomal mosaicism via genome-wide circulating cell-free maternal plasma DNA (cfDNA) screening.sponsorship: SymBio-Sys, Grant/Award Number: PFV/10/016; GOA, Grant/Award Number: GOA/12/015 (SymBio-Sys|PFV/10/016, GOA|GOA/12/015)status: Publishe
Simulation of Colloidal Stability and Aggregation Tendency of Magnetic Nanoflowers in Biofluids
No full textA population balance model for the aggregation of iron oxide nanoflowers (IONfs) is presented. The model is based on the fixed pivot technique and is validated successfully for four kinds of aggregation kernels. The extended Derjaguin, Landau, Verwey, and Overbeek (xDLVO) theory is also employed for assessing the collision efficiency of the particles, which is pertinent to the total energy of the interaction. Colloidal stability experiments were conducted on IONfs for two dispersant cases—aqueous phosphate buffered saline solution (PBS) and simulated body fluid (SBF). Dynamic light scattering (DLS) measurements after 24-h of incubation show a significant size increase in plain PBS, whereas the presence of proteins in SBF prevents aggregation by protein corona formation on the IONfs. Subsequent simulations tend to overpredict the aggregation rate, and this can be attributed to the flower-like shape of IONfs, thus allowing patchiness on the surface of the particles that promotes an uneven energy potential and aggregation hindering. In silico parametric study on the effects of the ionic strength shows a prominent dependency of the aggregation rate on the salinity of the dispersant underlying the effect of repulsion forces, which are almost absent in the PBS case, promoting aggregation. In addition, the parametric study on the van der Waals potential energy effect—within common Hamaker-constant values for iron oxides—shows that this is almost absent for high salinity dispersants, whereas low salinity gives a wide range of results, thus underlying the high sensitivity of the model on the potential energy parameters
Radish and Spinach Seedling Production and Early Growth in Response to Struvite Use as a Phosphorus Source
No full textTo sustain the increasing needs of a rapidly growing population, agriculture has relied on the use of synthetic fertilizers to intensify its production. However, the economical, environmental and health impacts associated with their use have raised significant concerns, especially given the scarcity of phosphorus. Utilizing nutrient-recovered materials like struvite can enhance circularity in agriculture and reduce its reliance on synthetic fertilizers. The objective of this study was to assess the implementation of struvite as a complete substitute to triple superphosphate, for radish and spinach seedling production and early growth, with or without supplementary fertigation. In addition, two rates of struvite were examined (0.68 and 1.37 g L−1 substrate) to evaluate its solubility. In the germination of radish, struvite had similar performance with conventional fertilization, while in spinach, the use of struvite decreased mean germination times. Both plants maintained comparable growth, chlorophyll content and antioxidant capacity when struvite was used, in comparison to conventional fertilizers. However, higher struvite rates under un-fertigated conditions significantly increased the chlorophyll b and total chlorophylls in the spinach, while phenolics and flavonoids decreased, contingent on the fertigation applications. In the radish, struvite maintained similar MDA and H2O2 levels to conventional fertilization, while decreases occurred in the spinach, with the application of ST1 under un-fertigated conditions, compared with conventional fertilization. The P and N contents of the plants were also affected, though these effects varied depending on the plant species, fertigation applications and struvite rates. This variance can be attributed to the characteristics of struvite, the plant species and the cultivation practices. The results of this study suggest that struvite can be successfully implemented in seedling production, establishing significant prospects for its commercialization and use in nurseries
Fertility status in childhood cancer survivors of hematological malignancies: a systematic review
No full textStunning advances in treatment modalities implemented in children with hematological malignancies have led to 5-year overall survival rates exceeding 85%. However, this growing population of long-term survivors has raised significant concerns about their fertility status throughout adulthood, while specific treatment- and non-treatment-related factors appear to possibly affect fertility through distinct mechanisms. We aimed to comprehensively review the published literature on the association between treatment-related factors and risk of impaired fertility in childhood hematological cancer survivors. We searched PubMed up to March 2021 to identify eligible studies published during the last two decades. A narrative synthesis of the results was performed, although no meta-analysis was feasible due to the small number of studies and the large heterogeneity of evidence. Five studies on 2020 survivors of childhood leukemia were deemed eligible. The qualitative data synthesis showed significant fertility deficits in survivors treated with cranial radiotherapy and chemotherapy for childhood leukemia. Two studies examined biochemical measures of reduced ovarian reserve, providing some evidence that the levels of anti-Müllerian hormone can be used as a proxy for diminished ovarian reserve. The current findings should facilitate the delivery of age- and gender-appropriate interventions to optimize reproductive outcomes in childhood hematological cancer survivors. © 2023, The Author(s), under exclusive licence to Hellenic Endocrine Society
