Biology subjects

Papadopoulou, V.

Publications and source records attributed to Papadopoulou, V..

8 recordsLinked to original sources

bioRxiv2026

Ultrasonic Detection of Venous Gas Emboli and Tissue Gas in Rodents: Toward Imaging Biomarkers for Decompression Stress

Introduction In humans, decompression sickness (DCS) risk assessment often relies on surrogate ultrasound detection of venous gas emboli (VGE). Rodents are widely used to study DCS and mortality, yet no established relationship exists between imaging and decompression outcomes. We exposed rats to dives with differing DCS risk and investigated whether ultrasound measurements reflected modeled DCS risk and revealed tissue-level manifestations of decompression stress. Methods Rats underwent dry saturation exposures to 700 KPA in a hyperbaric chamber while breathing either heliox (low-risk; pDCS = 0.1%) or air (high-risk; pDCS = 13%), where pDCS was estimated using an existing rodent DCS risk model. Following decompression, animals were anesthetized for serial cardiac and renal ultrasound imaging. Echocardiograms were evaluated for VGE using an ordinal scale. The mean grayscale intensity (arbitrary units, a.u.) was also quantified in renal region of interest (ROI). In a separate set of animals, histopathology was conducted to evaluate renal manifestations. Results Observed peak VGE grades increased with estimated DCS risk, from grade 1 at pDCS 0.1% to grade 2 at pDCS 13%. Multi-organ analysis found lower renal ROI echogenicity during periods of high VGE, with mean grayscale intensities of 67.0 a.u. and 60.7 a.u. for VGE grades 0-1 and 2-4, respectively. Renal histopathology identified round voids consistent with pre-mortem gas emboli. Conclusions VGE burden tracked with pDCS risk. The decrease in renal image intensity during high VGE may indicate ultrasound attenuation from acoustic shadowing caused by excess tissue gas bubbles. These findings advance the development of physiologically relevant imaging biomarkers of decompression stress.

bioengineering↗

bioRxiv2026

A quantitative approach to assess similarity between dives under the Buhlmann decompression algorithm constraints

Undersea and high-altitude operations regularly put operators at risk for decompression sickness (DCS), which is attributed to bubble formation and growth during decompression. DCS mitigation strategies are validated with empirical testing, often conducted in hyperbaric chambers, which provide precise control of the pressure-time profile. A degree of variability for study outcome is anticipated in both decompression sickness (DCS) and venous gas emboli (VGE) endpoints. Experimentation in a chamber offers precision, but is not always practical or operationally relevant, leading researchers to use open water for the dive exposure. Dive profile consistency may vary by diver skill level and environmental conditions, potentially introducing dive profile deviations, which may be a factor of individual variability. There does not exist a quantitative framework for evaluating dive profile consistency and quantifying deviations in open water studies. In this work, we evaluate existing dive profile metrics and propose a workflow to estimate dive profile deviations using the Buhlmann dissolved gas phase model. The dive profile metrics included depth and time-based calculations, as well as surface gradient factor, degree-of-conservatism and the root mean square error of the Buhlmann tissue compartments. We developed a set of simulated dive profiles and obtained a set of 40 open water dives previously collected by certified divers, both of which were used to evaluate performance of the dive profile metrics. Depth and time-based metrics offered sensitivity to varying depths and time durations of the dive profiles, respectively. For the field dives, we found the Buhlmann root mean square error metric performed best at identifying the deviation profile, followed by pressure root time. These evaluations demonstrate the utility and limitations of previously published dive profile metrics and emphasize the importance of accounting for dive profile consistency in open water decompression trials.

physiology↗

bioRxiv2026

Quantitative Ultrasound Analysis of Gas Embolic Disease in Bycaught Sea Turtles

ObjectivesBycatch-related decompression after forced submersion can result in severe gas embolic disease in sea turtles. This work used qualitative and quantitative ultrasound analyses, including gas grading, brightness analysis, and texture feature extraction, to investigate organ-specific gas burden and temporal evolution in the hearts, kidneys, and livers of bycaught sea turtles. Materials and MethodsUltrasound imaging of the hearts, kidneys, and livers of bycaught turtles was performed as part of veterinary evaluation either onboard fishing vessels immediately after surfacing (boat group, n=47) or after longer periods at shore-based facilities (shore group, n=30). Gas burden in each ultrasound scan was graded on an ordinal scale from 0 (no gas) to 5 (gas completely shadowing organ anatomy). Temporal differences in gas burden were compared between the shore and boat groups. Quantitative brightness and texture features were extracted from all organs, including contrast, correlation, homogeneity, and energy from liver and kidney data. A multivariate logistic regression model with leave-one-out cross-validation was conducted, with shore versus boat as a binary outcome (surrogate of post-surfacing decompression state) and ultrasound texture metrics as independent variables. ResultsMedian grades from the first ultrasound scan were significantly higher in the boat group than in the shore group for the liver, kidney, and heart (3, 3, and 3 vs 1, 1, and 0, respectively). This pattern coincided with a difference in the mean duration until the first scan which was conducted being 54 min for the onboard studies vs 330 minutes in the shore group. Mean pixel brightness within cardiac and liver regions of interest increased with rising bubble grade before decreasing at the highest grades, consistent with acoustic shadowing at severe gas burden. Texture features demonstrated significant organ-specific changes with increasing gas burden, and the regression models achieved areas under the receiver operating characteristic curve of 0.92 for liver texture features and 0.83 for kidney texture features. ConclusionsThese findings demonstrate organ-specific differences in gas evolution over time. Quantitative ultrasound features were associated with gas burden and post-surfacing interval in bycaught sea turtles. These findings support the feasibility of quantitative ultrasound biomarkers for assessment of decompression-related gas burden.

physiology↗

bioRxiv2026

Human decompression in real time: programmable ultrasound imaging during hyperbaric exposure

The formation of inert gas bubbles during decompression can lead to decompression sickness (DCS), a major operational risk for divers, compressed-gas workers, astronauts, and high-altitude aviators. In diving, DCS risk is typically inferred from post-dive ultrasound detection of venous gas emboli (VGE), precluding modification of decompression schedules based on real-time physiological feedback. Two-dimensional ultrasound imaging could provide additional insight into decompression-related physiological changes; however, its use in hyperbaric environments has been largely precluded by fire risk associated with elevated oxygen partial pressures (ppO2) in enclosed spaces. Here, we developed a workflow for operating a programmable ultrasound system under hyperbaric conditions and acquiring ultrasound data from the subclavian vein and calf muscle during decompression. A total of 42 dives were conducted by 26 individuals using a previously characterized dive profile to 132 feet seawater (FSW) for 20 min with 9 min of decompression. Three exposure conditions were evaluated: non-exercising, exercising, and a brief pause at 20 FSW during compression. Twelve dives included programmable ultrasound imaging during decompression. Post-dive VGE responses were consistent with prior reports while demonstrating substantial inter-individual variability and sensitivity to modest profile modifications. VGE were detected in the subclavian vein during decompression in two participants and subsequently confirmed by post-dive echocardiography. Calf muscle ultrasound brightness typically increased from pre-dive to decompression measurements, before decreasing below baseline in the 120 min post dive measurement period. These findings demonstrate the feasibility of programmable ultrasound imaging during human decompression and establish a practical framework for ultrasound operation under hyperbaric conditions. This approach may support future physiological studies and development of automated decompression monitoring technologies. New and NoteworthyThis study demonstrates the first use of a programmable ultrasound system to acquire and quantitatively analyze ultrasound data during human decompression. The approach enabled direct visualization of venous gas emboli during decompression and revealed calf muscle ultrasound signal changes, providing a new tool for investigating physiological responses during decompression that are not accessible through conventional post-dive monitoring.

physiology↗

bioRxiv2025

A regulatory loop regulating signaling between LRRK2 and PP2A in cellular models of Parkinsons disease

Mutations in Leucine-rich repeat kinase 2 (LRRK2) are the most frequent cause of late-onset familial and idiopathic Parkinsons disease (PD), known to date. Importantly, recent data from post-mortem tissue as well as biomarker studies suggest that independent of mutations, increased kinase activity of LRRK2 plays an essential role in idiopathic PD pathogenesis. Despite extensive research on LRRK2, its activation mechanism(s) and how the various mutations result in increased kinase activity and neuronal death is still not completely understood. Accumulating evidence points to LRRK2 phospho-regulation, both auto-phosphorylation and phosphorylation by other kinases, as one potential molecular trigger of its activation. LRRK2 activation and localization is regulated by phosphatases such as Protein phosphatase 1 (PP1) and Protein phosphatase 2A (PP2A), however the exact mechanism of this phospho-regulation is not known. Our data reveal that in vitro PP2A dephosphorylates sites within the RocCOR-GTPase domain of LRRK2 and as a result de-stabilizes LRRK2 dimers, with consequent reduction of its kinase activity. Strikingly, our data further highlight that LRRK2 in turn phosphorylates the catalytic subunit of the PP2A holoenzyme PPP2CA at its critical residue T304. Furthermore, LRRK2-mediated phosphorylation of PP2CA T304 alters the methylation of the C-terminus, which is crucial for both holoenzyme formation and catalytic activity. Importantly, expression of WT-PPP2CA protects from LRRK2-G2019S induced neuronal cell death, while PPP2CA-T304 mutants fail to do so, suggesting that impaired PP2A holoenzyme formation might be detrimental for LRRK2-PD.

neuroscience↗

bioRxiv2025

Genetic affinities between an ancient Greek colony and its metropolis: the case of Amvrakia in western Greece

BackgroundDuring the Ancient Greek colonization, Corinth established a stable network of economic and political ties, by founding colonies connecting southern Greece with the mainland of Epirus and reaching as far as the east Adriatic coast. Amvrakia, one of the main Corinthian colonies founded during the 7th century BCE, was characterized by its strong dependence on its metropolis. Here, we aim to investigate the genetic relationships between the Corinthian metropolis and the Amvrakia colony, the contribution of the local population to the founding genetic pool, as well as the demography of Amvrakia in subsequent periods. ResultsDuring its foundation in the Archaic period, Amvrakia appears to have been shaped by genetic influences from at least two different sources. The first source migrated from the Corinth territory, represented by the Archaic Tenea population and is supported via an Identity By Descent (IBD) analysis. The second source shows a direct ancestry from Late Bronze Age (LBA) / Iron Age Greece, including a local LBA population represented by the Ammotopos site located in close proximity to Amvrakia, as shown by a plethora of independent population genomics analyses. During the subsequent Classical and Hellenistic periods, the population of Amvrakia appears to have slightly differentiated, yet evidence of genetic continuity over time is observed. ConclusionsThe migration of Corinthians to Amvrakia contributed to the initial genetic pool of the colony along with the local genetic pool, indicating that the Corinthian colonization included both genetic and cultural transmission between the metropolis and its colony.

evolutionary biology↗

bioRxiv2020

Contrast-enhanced sonography with biomimetic lung surfactant nanodrops

Nanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides distinct advantages, including in situ activation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilizing an expanding gas surface by employing the lung surfactant replacement, Beractant. Lung surfactant contains a suite of lipids and surfactant proteins that provides efficient shuttling of material from bilayer folds to the monolayer surface. We therefore hypothesized that Beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized Beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading and re-solidification. We then harnessed this unique spreading capability to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization for in vivo ultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/367235v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@b6b2f4org.highwire.dtl.DTLVardef@9eb8b7org.highwire.dtl.DTLVardef@71364corg.highwire.dtl.DTLVardef@a3c41d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2020

Harnessing Ultrasound-Stimulated Phase Change Contrast Agents to Improve Antibiotic Efficacy Against Methicillin-Resistant Staphylococcus aureus Biofilms

Bacterial biofilms, often associated with chronic infections, respond poorly to antibiotic therapy and frequently require surgical intervention. Biofilms harbor persister cells, metabolically indolent cells, which are tolerant to most conventional antibiotics. In addition, the biofilm matrix can act as a physical barrier, impeding diffusion of antibiotics. Novel therapeutic approaches frequently improve biofilm killing, but usually fail to achieve eradication. Failure to eradicate the biofilm leads to chronic and relapsing infection, associated with major financial healthcare costs and significant morbidity and mortality. We address this problem with a two-pronged strategy using 1) antibiotics that target persister cells and 2) ultrasound-stimulated phase-change contrast agents (US-PCCA), which improve antibiotic penetration. We previously demonstrated that rhamnolipids, produced by Pseudomonas aeruginosa, could induce aminoglycoside uptake in gram-positive organisms, leading to persister cell death. We have also shown that US-PCCA can transiently disrupt biological barriers to improve penetration of therapeutic macromolecules. We hypothesized that combining antibiotics which target persister cells with US-PCCA to improve drug penetration could eradicate methicillin resistant S. aureus (MRSA) biofilms. Aminoglycosides alone or in combination with US-PCCA displayed limited efficacy against MRSA biofilms. In contrast, the anti-persister combination of rhamnolipids and aminoglycosides combined with US-PCCA dramatically reduced biofilm viability, frequently culminating in complete eradication of the biofilm. These data demonstrate that biofilm eradication can be achieved using a combined approach of improving drug penetration of therapeutics that target persister cells.

microbiology↗