Biology subjects

Sharon, O.

Publications and source records attributed to Sharon, O..

7 recordsLinked to original sources

bioRxiv2026

Intubation and mechanical ventilation lead to an extensive expansion of VAP-associated bacterial species in respiratory secretions of ventilated pigs

Ventilator associated pneumonia (VAP) remains one of the most critical nosocomial infections in intensive care medicine. Between 20-50% of ventilated patients develop VAP during treatment, often leading to long term sequelae and death, despite successful therapy of their underlying disease. VAP is typically caused by Gram-negative bacteria that can previously be detected on the mucosal membranes of the oral and upper respiratory tract. To assess and quantify bacterial colonization of the respiratory tract following intubation and ventilation a well-established pig model was used. Methods: After induction of anaesthesia and endotracheal intubation pigs underwent mechanical ventilation continuously for up to three days. To assess bacterial colonization of the upper respiratory tract, samples of respiratory secretions were taken at day 0, 1 and 2 directly above the cuff outside of the endotracheal tube (ETT) and by aspiration of tracheal secretions through the ETT. Quantification of bacteria was carried out by serial dilutions and CFU/ml determinations on sheep blood agar and MacConkey agar plates. Species identification was achieved by 16S-RNA gene sequencing. Results: Respiratory samples of 19 pigs were analysed and showed a sharp increase of predominantly Gram-negative organisms in the respiratory material sampled above the cuff from day 0 to 1. Starting at a median of 7.3 x 103 immediately after intubation numbers increased to a median of 2.0 x 107 Gram-negative bacteria at day 1 and 3.2 x 107 at day 2. Gram-negative species that were detected included Pseudomonas aeruginosa, Acinetobacter baumanii, Enterobacter aerogenes, Klebsiella pneumoniae and other Enterobacteriaceae. Tracheal secretions contained much less bacteria. While no Gram-negative bacteria could be cultured at the beginning of the experiment in 18 of 19 animals, colonization with Gram-negative bacteria gradually increased and was found in 7 of 19 and 9 of 14 animals on day 1 and day 2 respectively. Interestingly, in the vast majority of colonized tracheal secretions the identical Gram-negative species had previously been detected in secretions collected > 24h earlier at the cuff. Conclusion: A massive increase of the concentration of Gram-negative bacteria occurred at 24h of ventilation in mucosal secretions above the cuff. Detected species were the same Gram-negative bacteria that are frequently responsible for human infections, suggesting that especially the accumulation of bacteria in secretions above the cuff may be crucial in the development of VAP.

microbiology↗

bioRxiv2025

REM Sleep Misfires: Intruding Delta Waves Forecast Tau, Amyloid, and Forgetting in Aging

Rapid Eye Movement (REM) sleep degrades with age, and more severely in Alzheimers disease (AD). REM sleep comprises about twenty percent of adult sleep, alternates between phasic and tonic periods, and includes delta waves (1-4Hz) in two forms: fast sawtooth waves and slower, NREM-like waves, whose expression dynamically varies across REM periods. Yet, the functional relevance of these REM sleep delta waves remains unknown. Here, using two independent cohorts, we show that aging is associated with a shift from fast sawtooth to slow NREM-like delta waves, particularly during phasic REM sleep--a period typically marked by high cortical activation. Beyond chronological age, this shift is associated with amyloid-beta and tau burden, suggesting that AD pathology disrupts REM-specific oscillatory patterns. Furthermore, this shift in REM oscillations is linked to impaired overnight memory consolidation, independent of NREM sleep quality. Moreover, variation in ApoE alleles, a major genetic risk factor for AD, was independently associated with a reduction in fast sawtooth wave density, thereby linking a genetic predisposition for AD to these specific REM microstructural changes. These findings identify a novel signature of memory decline in aging and implicate REM sleep as a distinct vulnerable substrate through which AD pathology may impair brain function.

neuroscience↗

bioRxiv2024

Seeing the Future: Anticipatory Eye Gaze as a Marker of Memory

Human memory is typically studied by direct questioning, and the recollection of events is investigated through verbal reports. Thus, current research confounds memory per-se with its report. Critically, the ability to investigate memory retrieval in populations with deficient verbal ability is limited. Here, using the MEGA (Memory Episode Gaze Anticipation) paradigm, we show that monitoring anticipatory gaze using eye tracking can quantify memory retrieval without verbal report. Upon repeated viewing of movie clips, eye gaze patterns anticipating salient events can quantify their memory traces seconds before these events appear on the screen. A series of five experiments with a total of 145 participants using either tailor-made animations or naturalistic movies consistently reveal that accumulated gaze proximity to the event can index memory. Machine learning-based classification can identify whether a given viewing is associated with memory for the event based on single-trial data of gaze features. Detailed comparison to verbal reports establishes that anticipatory gaze marks recollection of associative memory about the event, whereas pupil dilation captures familiarity. Finally, anticipatory gaze reveals beneficial effects of sleep on memory retrieval without verbal report, illustrating its broad applicability across cognitive research and clinical domains.

neuroscience↗

bioRxiv2024

Tau pathology leads to lonely non-traveling slow waves that mediate human memory impairment

Memory markedly declines with age, exaggerated in those with Alzheimers disease, yet the mechanisms are still not resolved. Here, we show that frontal lobe tau pathology in humans leads to impaired en masse unity and cortical traveling propagation of NREM slow waves, consequentially impairing memory retention. We elucidate these findings using PET tau brain imaging, and then replicate and extend them using AD pathology markers derived from lumbar puncture CSF in an independent clinical cohort. Thus, tau-associated memory deficits are not wholly direct, but indirectly mediated through consequential "lonely", non-traveling slow-wave events.

neuroscience↗

bioRxiv2023

A visual paired associate learning (vPAL) paradigm to study memory consolidation during sleep

The hippocampus helps transform an experience into an enduring memory by associating its multiple aspects. Sleep improves the consolidation of the newly formed associations, leading to stable long-term memory. Most research on human declarative memory and its consolidation during sleep uses word-pair associations requiring exhaustive learning. Here we present the visual paired association learning (vPAL) paradigm, in which participants learn new associations between images of celebrities and animals. vPAL associations are based on a one-shot exposure that resembles learning in natural conditions. We tested if vPAL can reveal a role for sleep in memory consolidation by assessing the specificity of memory recognition, and the cued recall performance, before and after sleep. We found that a daytime nap improved the stability of recognition memory and discrimination abilities compared to identical intervals of wakefulness. By contrast, cued recall of associations did not exhibit significant sleep-dependent effects. High-density EEG during naps further revealed an association between sleep spindle density and stability of recognition memory. Thus, the vPAL paradigm opens new avenues for future research on sleep and memory consolidation across ages and heterogeneous populations in health and disease.

neuroscience↗

bioRxiv2022

The role of vertical and horizontal transmission in the assembly of seed fungal endophyte communities in wheat and wheat wild relatives

Plants acquire fungal endophytes either from the environment or from their progenitors. These transmission modes are central in shaping the community as they affect species composition and balance. We studied fungal endophyte communities (FEC) and their seed-to-seed transmission in three Triticeae plant species: bread wheat (Triticum aestivum), wild emmer wheat (Triticum turgidum dicoccoides) and wild barley (Hordeum spontaneum). The FECs in the three plant species contained similar fungal taxa, however they were overall different. The most prevalent class of fungi was Dothideomycetes, which was dominated by the taxon Alternaria infectoria. In field collected plants, the number of taxa in the seeds was less than half the number in stems, with close to 90% of the taxa found in seeds also found in stems. Growing the same plant species in a controlled environment infection greatly affected their FEC composition; the FECs in the stems and seeds of these plants were richer and more diverse than in the original seeds, they were not dominated by a single taxon, and FECs in the new seeds had a similar richness and diversity to the stem FECs, with only 40% overlap. The controlled environment experiment confirmed vertical transmission of certain species, but also showed that external infection of the seeds is the main source for specific taxa, including A. infectoria. Collectively, our results show that many taxa can reach the seeds through the internal pathway, albeit in different abundance, and both internal and external sources significantly affect the composition of seed FECs.

plant biology↗

bioRxiv2020

Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations

Vagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS), which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent that tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS. Significance statementCurrent non-invasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating-current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4s) tVNS pulses in naive healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus-noradrenaline signaling, and support the notion that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying the means by which endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.

neuroscience↗