Biology subjects

Florea, C.

Publications and source records attributed to Florea, C..

8 recordsLinked to original sources

bioRxiv2026

Talking Brains: Neonatal Aperiodic Activity in Resting State EEG Relates to Later Communicative Abilities

Communicative abilities acquired over the first year of life are foundational for language development. Understanding the neural mechanisms underlying these abilities can explain individual differences and improve predictions of later language outcomes. While prior research on neural markers of language development has focused predominantly on oscillatory neural activity, the underlying aperiodic component of the neural signal may provide further insights into cortical maturation by indirectly reflecting variation in neural excitation/inhibition (E/I) balance. In neurodevelopmental conditions, both reduced and elevated aperiodic activity are linked to atypical development, and initial evidence from at-risk cohorts also relates aperiodic activity to language outcome. Moving beyond clinical populations, the present study examined whether aperiodic activity during neonatal resting-state EEG relates to 12-month communicative abilities in typically developing infants. Aperiodic offset and exponent were extracted from resting-state EEG recorded two weeks after birth in n = 50 neonates using the FOOOF algorithm. At 12 months, communicative abilities were assessed with the parent-report CSBS-DP Infant-Toddler Checklist. Quadratic regression analyses showed an inverted U-shaped relationship between the neonatal aperiodic exponent and communicative abilities: both lower and higher exponent values were associated with poorer outcomes, with intermediate values linked to better abilities. No robust association was found for the offset. These findings suggest that aperiodic activity captures variability in early communicative development, with an optimum at intermediate levels, consistent with a balanced E/I state. The scope of aperiodic brain activity as a developmental marker may thus extend beyond clinical populations to predicting communicative development in healthy infants.

developmental biology↗

bioRxiv2026

A computational framework to model cartilage degeneration induced by mechanoinflammation and cytokine-driven inflammation in post-traumatic osteoarthritis

Knee joint injury is a major risk factor for post-traumatic osteoarthritis (PTOA), often associated with early cartilage degeneration. Mechanical overloading and cytokine-driven inflammation are key drivers of this process, yet the underlying mechanisms and their distinct temporal and spatial contributions to cartilage degradation remain unclear. Here, we present a mechanobiological finite element framework that simulates cartilage degradation through cell-mediated proteolytic activity triggered by mechanoinflammation and cytokine-driven inflammation. The model reproduces experimentally observed depth-dependent loss of collagen and aggrecan, with mechanoinflammation inducing a transient response and cytokine-driven inflammation sustaining prolonged matrix degradation. Sensitivity analysis further shows that mechanoinflammation-driven degradation is governed mainly by protease production per cell, whereas cytokine-driven degradation is more sensitive to the rate of cellular stimulation. Together, this framework provides a mechanistic basis to study proteolytic cartilage degeneration and supports future in silico evaluation of therapeutic strategies aimed at mitigating cartilage degradation in PTOA.

biophysics↗

bioRxiv2026

From Variability to Synchrony: Non-linear Development of Auditory Neural Responses During the First Year of Life

In humans, the first year of life is characterized by rapid developmental changes, including substantial brain maturation. As a result, neural responses to auditory stimuli undergo marked changes during this period. In this study, we followed 69 infants across their first year of life and recorded high-density electroencephalography (hdEEG) at 2 weeks, 6 months, and 12 months postpartum. Infants were presented with pure beep tones to examine the development of neural responses to auditory stimulation. We analysed event-related potentials (ERPs), inter-trial phase coherence (ITPC), and time-frequency (TF) responses to the beep tones and controlled for arousal state during stimulus presentation. We found that with increasing age, neural responses became more pronounced and showed reduced trial-to-trial variability. Phase synchronization increased from 2 weeks to later developmental stages in a broad low-frequency range (0 to 11 Hz), indicating improved temporal alignment of brain responses over time. However, phase synchronization decreased from 6 to 12 months, suggesting a developmental transition towards more differentiated brain activity. Taken together, these findings demonstrate that auditory maturation during the first year of life follows a non-linear trajectory driven by dynamic changes in neural synchronization, reflecting the progressive refinement of functional neural circuits. Our results thus provide a critical benchmark for understanding the neural dynamics underlying sensory development during this period.

developmental biology↗

bioRxiv2025

Fetal Dehydroepiandrosterone from Hair Samples at Birth Predicts Language Development

ObjectiveSex hormones testosterone and estradiol have been related to childrens language development. Expanding the focus on dehydroepiandrosterone (DHEA), which has not yet been considered as a biological marker of language ability, may provide novel insights, as emerging evidence suggests that fetal DHEA plays a critical role in the organization of the neonatal brain, potentially shaping later language development. The present study investigated whether fetal DHEA, compared to fetal testosterone, is associated with infant language development. Design and methodsDHEA and testosterone concentrations were measured in newborn hair strands (n = 63) collected two weeks after birth, capturing fetal long-term hormone secretions during the third trimester of pregnancy. At six months of age, childrens language abilities were assessed using the German version of the Bayley Scales of Infant Development. Results. Linear regression analysis revealed fetal DHEA levels to be significantly associated with language abilities at six months of age, with lower DHEA levels corresponding to higher language scores. Control analyses assessing general cognitive abilities showed no association of fetal DHEA levels with infant cognitive function. Testosterone levels were not associated with language. ConclusionsThe current study identifies fetal DHEA levels extracted from newborn hair samples as a potential biological factor influencing infant language development.

developmental biology↗

bioRxiv2025

MMP release following cartilage injury leads to collagen loss in intact tissue - a computational study

Damage of collagen fibril network in articular cartilage plays a key role in post-traumatic osteoarthritis but the main underlying mechanobiological mechanisms of fibrils degeneration early after injury are not fully understood. This study explores the hypothesis that injurious loading leads to cellular damage that triggers the release of matrix metalloproteinases (MMPs), resulting in loss of collagen content in cartilage. To investigate this, we developed a computational mechano-signaling model simulating spatial collagen loss in bovine cartilage. In the model, the injurious loading causes excessive shear strains in tissue matrix, leading to cell damage and subsequent release of MMPs. The model was compared to ex vivo cartilage explant experiments over 12 days post-injury where collagen content was assessed via Fourier-transform infrared microspectroscpy. By day 12, the simulated collagen loss aligned with our experimental findings along most of tissue depth ([~]30% bulk average loss in the model vs. [~]35% in the experiment). The results suggest that injury-related cell damage and the downstream MMP activity could partly explain the depth-wise collagen content loss in early days after ex vivo cartilage injury. Ultimately, combining the current approach with joint-level computational models could enhance the prediction of the onset and progression of cartilage degeneration. Author SummaryKnee injuries can initiate an irreversible degeneration of articular cartilage which can later lead to the development of post-traumatic osteoarthritis over the years. Currently, there is no cure or effective intervention to repair degenerated cartilage or halt disease progression. Yet, opportunities for intervention depend on a thorough understanding of mechanisms that govern the very early changes in cartilage tissue composition such as the collagen fibrils. In this work, we developed a finite element computational modeling framework to simulate cartilage following injurious loading, focusing on the early loss of collagen content. The model aims to capture the role of injury-induced cellular damage in elevating proteolytic activity within the tissue, which could rapidly degrade collagen fibrils and result in significant collagen loss. This model framework offers a tool for studying the degradation of the collagen fibril network, testing hypotheses involving cell-driven mechano-signalling pathways and evaluating potential treatment interventions aimed at preventing collagen loss.

biophysics↗

bioRxiv2024

Time-dependent computational model of post-traumatic osteoarthritis to estimate how mechanoinflammatory mechanisms impact cartilage aggrecan content

Degenerative musculoskeletal diseases like osteoarthritis can be initiated by joint injury. Injurious overloading-induced mechanical straining of articular cartilage and subsequent biological responses may trigger cartilage degradation. One early sign of degradation is loss of aggrecan content which is potentially accelerated near chondral lesions under physiological loading. Yet, the mechanoinflammatory mechanisms explaining time-dependent degradation in regions with disparate mechanical loading are unclear and challenging to assess with experiments alone. Here, we developed computational models unraveling potential mechanisms behind aggrecan content adaptation. Incorporating mechanical strain-driven cell damage and downstream proteolytic enzyme release, fluid flow-driven aggrecan depletion, and fluid pressure-stimulated regulation of aggrecan biosynthesis, the models agreed with experiments and exhibited 14%-points greater near-lesion aggrecan loss after 12 days of physiological loading compared to without loading. This significant advancement in mechanistic understanding incorporated into cartilage adaptation model can help in development and guidance of personalized therapies, such as rehabilitation protocols and tissue- engineered constructs.

bioengineering↗

bioRxiv2024

Neural speech tracking in newborns: prenatal learning and contributing factors

IntroductionEarly language development in infants is being increasingly studied, though only recently with direct measurements of brain activity rather than with behavioral or physiological measurements. In the current study, we use electroencephalographic (EEG) recordings of 2-week-old infants to look for signs of prenatal learning and to investigate newborns abilities to process language. We also look at the influence of prenatal stress factors and at the predictive value of the newborns language processing abilities for later language development. MethodsSixty pregnant women played a rhyme to their abdomen twice a day from the 34th week of pregnancy until birth, to familiarize the fetus with the rhyme. At around 2 weeks after delivery (mean age 16 days), the newborns were exposed to the familiar rhyme as well as to an unfamiliar one while their EEG was recorded. Additionally, three manipulations of the familiar rhyme were played: (1) low-pass filtered, (2) with changed rhythm, and (3) inverted and played backwards. The data was analyzed to see how well the infant brain signal followed the speech envelope in each condition. Accounting for the heterogenous approach used for neural speech tracking in the literature, we used four methods, namely: (1) coherence, (2) Hilbert coherence, (3) temporal response functions (TRF), and (4) mutual information (MI). The maternal prenatal depression was evaluated with Edinburgh Prenatal Depression Score and the chronic fetal stress was measured from the hair cortisol levels of the 2 week-olds. The language development at 6 months of age was evaluated with the Bayley Scales. Results and discussionOverall, the results indicate the presence of prenatal learning, with the unfamiliar rhyme eliciting stronger cortical tracking (higher coherence and MI) than the familiar rhyme, which suggests stronger brain-to-speech coupling for the unfamiliar rhyme, perhaps deriving from more effort to process the unexpected stimulus. However, the original version of the familiar rhyme proved to be the easiest to track compared to the language- and rhythm-manipulations, (higher MI for the original rhyme than the language manipulation and higher coherence and mTRF correlation coefficients for the original rhyme than the rhythm manipulation). This indicates language discrimination and a prosodic-based learning of the familiar rhyme. Furthermore, there is an indication of phonotactic sensitivity at this young age, with less tracking (lower Hilbert coherence and lower mTRF correlation coefficients) of the low-pass filtered rhyme than the original version, indicating that the phonological cues erased by the filtering were important for the newborns ability to follow the rhyme. Furthermore, the mothers depression scores positively correlated with the infants tracking ability for the familiar rhyme. This suggests that a slightly lower mood was more stimulative for the fetal language development. The chronic fetal stress levels, however, were negatively correlated with the cortical tracking abilities. Importantly, the newborns cortical tracking was positively correlated with the infants language development at 6 months of age, underlining the predictive value of the early assessment of language processing. ConclusionPrenatal learning is well established, but evidence including (healthy) brain data in the first weeks of life is scarce. The current study shows that newborns can discriminate between a familiar and unfamiliar rhyme, while also highlighting the role of prosody in early language processing, and bringing new evidence of their sensitivity to phonotactic cues in auditory stimuli. Furthermore, the newborns ability to track a rhyme is correlated with their language development at 6 months. The newborns cortical tracking of the familiar rhyme is further increased by moderately low maternal mood, but decreased by fetal stress. Future studies with similar fine-grained linguistic designs but of older infants should teach us the timeline of what exactly is learned prenatally and at very early age in respect to language.

developmental biology↗

bioRxiv2021

Cyclic loading regime considered beneficial does not protect injured and interleukin-1-inflamed cartilage from post-traumatic osteoarthritis

Post-traumatic osteoarthritis is a degenerative musculoskeletal condition where homeostasis of articular cartilage is perturbated by lesions and inflammation, leading to abnormal tissue-level loading. These mechanisms have rarely been included simultaneously in in vitro osteoarthritis models. We modeled the early disease progression in bovine cartilage regulated by the coaction of (1) mechanical injury, (2) pro-inflammatory interleukin-1 challenge, and (3) cyclic loading mimicking walking and considered beneficial (15% strain, 1 Hz). Surprisingly, cyclic loading did not protect cartilage from accelerated glycosaminoglycan loss over 12 days of interleukin-1-culture despite promoting aggrecan biosynthesis. Our time-dependent data suggest that this loading regime could be beneficial in the first days following injury but later turn detrimental in interleukin-1-inflamed cartilage. Consequently, early anti-catabolic drug intervention may inhibit, whereas cyclic loading during chronic inflammation may promote osteoarthritis progression. Our data on the early stages of post-traumatic osteoarthritis could be utilized in the development of countermeasures for disease progression.

pathology↗