Biology subjects

Christodoulou, M.

Publications and source records attributed to Christodoulou, M..

4 recordsLinked to original sources

bioRxiv2025

Ecology of Echinodermata in the Clarion-Clipperton-Fracture Zone (Central Pacific)

Abyssal seascapes between 3,000 and 6000 m water depth represent over 50% of the Planets surface, but the species, functions, and particularly the life history traits that these ecosystems harbour remain poorly understood. Brittle stars (Ophiuroidea) contribute about one third to the invertebrate megabenthos assemblage between 3,800 m and 4,800 m water depth in the Clarion-Clipperton Fracture Zone (CCZ, Northeast Pacific). Starfishes (Asteroidea) are present in lower densities. In the CCZ, Ophiuroidea are often seen near Xenophyophoroidea and attached to glass sponge (Hexactinellida) stalks. We hypothesize that (1) the observed relationship between Ophiuroidea, Xenophyophoroidea, and Hexactinellida is a predator-prey relationship, where Ophiuroidea feed on foraminifera- and sponge-derived organic matter. (2) Ophiuroidea have a reduced dependency on fresh phytodetritus. (3) Brisingida (order of Asteroidea), often clings to stalks to have easier access to particulate organic matter sinking to the seafloor. To test these three hypotheses, we combined bulk and compound-specific stable isotope analyses of fauna (Ophiuroidea, Asteroidea) and sediments with the analyses of seafloor images from the eastern CCZ. Faunal specimens and sediments were collected during three research expeditions between 2019 and 2022, and previously collected seabed images were re-analysed to quantify the major behaviours in which Ophiuroidea and Asteroidea engage. All investigated Echinodermata species had a high trophic level. Phospholipid-derived fatty acids (PLFAs) used as biomarkers suggest that Silax daleus consumes sedimentary detritus that is processed by its gut microbiome. Ophiacantha cosmica is likely a top consumer or scavenger, Ophiosphalma glabrum is an opportunistic omnivore ingesting phytodetritus, bacteria, Crustacea, and Foraminifera, while Ophiuroglypha cf. polyacantha is a more selective omnivore. Freyella benthophila sits mostly on stalks of Hexactinellida and uses this elevated position to catch phytodetritus and zooplankton. Freyastera cf. tuberculata, in comparison, sits mostly on polymetallic nodules from where it preys upon Crustacea moving on the sediment surface. This study confirmed the hypothesis that Ophiuroidea in the CCZ are less dependent on phytodetritus than Holothuroidea in the Peru Basin. It was confirmed that Ophiuroidea consume foraminifera- and sponge-derived organic matter, but Brisingida cling to stalks of Hexactinellida to prey upon Crustacea living in the benthic boundary layer.

ecology↗

bioRxiv2024

Antibacterial activity of tamoxifen derivatives against methicillin-resistant Staphylococcus aureus

The present work aimed to discover new tamoxifen derivatives with antimicrobial potential, particularly targeting methicillin-resistant Staphylococcus aureus (MRSA). The MIC of 22 tamoxifen derivatives was determined against S. aureus reference and MRSA strains, using microdilution assays. The antibacterial effects of selected tamoxifen derivatives against MRSA (USA7) were assessed through bacterial growth assays. Bacterial membrane permeability and molecular docking assays were performed. The MIC of the tamoxifen derivatives against MRSA ranged from to 16 to >64 g/mL. Bacterial growth assays demonstrated that tamoxifen derivatives 2, 5, and 6 reduced dose-dependently the growth of the USA7 strain. Moreover, treatment of MRSA with derivatives 2 and 5 resulted in increased membrane permeabilization without being the cell wall their molecular target. These data suggest that tamoxifen derivatives exhibit antibacterial activity against MRSA, potentially broadening the spectrum of available drug treatments for combating antimicrobial-resistant Gram-positive bacteria. ImportanceThe development of new antimicrobial therapeutic strategies requires immediate attention to avoid the tens of millions of deaths predicted to occur by 2050 as a result of multidrug-resistant (MDR) bacterial infections. In this study, we assessed the antibacterial activity of 22 tamoxifen derivatives against methicillin-resistant Staphylococcus aureus (MRSA). We found that three tamoxifen derivatives exhibited antibacterial activity against MRSA clinical isolats, presenting MIC50 values between 16 and 64 g/mL and reducing bacterial growth over 24 h. Additionally, this antibacterial activity for two of the derivatives was accompanied by increased membrane permeability of MRSA. Our results suggest that tamoxifen derivatives might be used as a potential therapeutic alternative for treating MRSA strains in an animal model of infection.

microbiology↗

bioRxiv2023

The FSGS disease gene product and nuclear pore protein NUP205 regulates nuclear localization and activity of the transcriptional regulators YAP and TAZ in podocytes

BackgroundMutations in genes encoding nuclear pore proteins (NUPs) cause steroid-resistant nephrotic syndrome (SRNS) and focal and segmental glomerulosclerosis (FSGS). The mechanisms of how NUP deficiency may cause podocyte dysfunction and failure of the kidney filtration barrier are elusive. The tightly controlled activity of the transcriptional effectors of the evolutionarily conserved Hippo pathway YAP and TAZ is essential for podocyte homeostasis. Here we analyze the role of NUPs in controlling YAP/TAZ nuclear import and activity in podocytes. MethodsWe used quantitative label-free mass spectrometry to characterize the YAP/TAZ interactomes in podocytes, particularly identifying NUP interactions. Moreover, we specifically studied NUP205 in controlling YAP/TAZ nuclear import and YAP/TAZ-dependent target gene expression. ResultsHere we identify the disease-causing nuclear pore proteins NUP107, NUP133, NUP205, and XPO5 as components of YAP and TAZ protein complexes in podocytes. We demonstrate that NUP205 is essential for YAP/TAZ nuclear import. The nuclear interaction of YAP/TAZ with TEAD1 and their transcriptional activity were dependent on NUP205 expression. Furthermore, we identify a feedback regulatory mechanism that controls YAP activity depending on TAZ-mediated NUP205 expression. ConclusionThis study links the disease protein NUP205 with the activity of the transcriptional regulators and Hippo effectors YAP and TAZ and suggests a pathogenic role of YAP/TAZ-deregulation in podocytes in patients with NUP205 mutations. Moreover, this study suggests an important role of YAP/TAZ signaling in human FSGS. SIGNIFICANCE STATEMENTUnderstanding the interference of signaling pathways in genetic diseases is essential to finally develop tailored treatment strategies. The increasing number of pathogenic variants causing focal-segmental glomerulosclerosis (FSGS) comprises genes encoding for proteins of the nuclear-cytoplamic shuttling machinery. We here found several of these proteins in an unbiased interactome analysis of the Hippo signaling effector proteins YAP and TAZ in podocytes, pointing to a connection between nucleoporins and the Hippo pathway. Further analyses confirmed that NUP205 is essential for correct YAP/TAZ shuttling; depletion of NUP205 resulted in cytoplasmic retention and inactivation of YAP/TAZ. We suggest the nuclear pore and hippo signaling as a pathogenic module in FSGS.

cell biology↗

bioRxiv2021

Comparative reproductive biology of deep-sea ophiuroids inhabiting polymetallic-nodule fields in the Clarion-Clipperton Fracture Zone

Deep-sea mining in the Pacific Clarion-Clipperton Fracture Zone (CCZ), a low-energy sedimentary habitat with polymetallic nodules, is expected to have considerable and long-lasting environmental impact. The CCZ hosts extraordinarily high species diversity across representatives from all Domains of Life. Data on species biology and ecology remain scarce, however. The current study describes the reproductive biology of Ophiosphalma glabrum (Lutken & Mortensen, 1899) (Ophiosphalmidae) and Ophiacantha cosmica (Lyman, 1878) (Ophiacanthidae), two ophiuroids frequently found in the CCZ. Specimens collected in Spring 2015 and 2019 in four contract areas were examined morphologically and histologically. Size-class frequencies (disc diameter and oocytes feret diameters), sex ratios, gametogenic status, putative reproductive mode and a simple proxy for fecundity are presented. Habitat use differs in each. While Ophiosphalma glabrum is epibenthic, occurring as single individuals, Ophiacantha cosmica often form size-stratified groups living on stalked sponges, suggesting gregarious settlement or retention of offspring (though no brooding individuals were found). Further molecular analyses are needed to establish whether O. cosmica groups are familial. In Ophiosphalma glabrum, for which sample sizes were larger, sex ratios approximated a 1:1 ratio with no size-structuring. In both species, individuals were at various stages of gametogenic maturity but no ripe females were identified. Based on this, O. glabrum is most probably gonochoric. Reproductive mode remains inconclusive for Ophiacantha cosmica. Both species are presumptively lecithotrophic, with vitellogenic-oocyte feret diameters exceeding 250 {micro}m. Oocyte feret diameters at times exceeded 400 {micro}m in Ophiosphalma glabrum, indicating substantial yolk reserves. Estimates of instantaneous fecundity (vitellogenic specimens of O. glabrum only) were confounded by interindividual variability in gonad characteristics. The well-furnished lecithotrophic larvae of O. glabrum would be capable of dispersing even under food-impoverished conditions. The current study examines ophiuroid reproductive biology over multiple localities in the CCZ concurrently for the first time, at sites characterised by differing productivity regimes. The reproductive biology of each species is thus discussed with reference to past evolutionary (habitat stability), contemporary (food supply) and future environmental drivers (potential impacts of deep-sea mining).

ecology↗