Biology subjects

Cecere, R.

Publications and source records attributed to Cecere, R..

4 recordsLinked to original sources

bioRxiv2025

Patient-Specific 3D Heart-On-a-Chip Model of Dilated Cardiomyopathy with Embedded Bead-Based Mapping of Tissue Contractility

Dilated cardiomyopathy (DCM) is the leading cause of heart transplantation, with a 50% risk of progression to heart failure within five years. Conventional disease modeling approaches fail to recapitulate the sophisticated function of the human heart. Alternatively, heart-on-a-chip (HOC) platforms enable real-time monitoring of disease progression and drug responses using miniaturized engineered heart tissues. Here, we developed a functional HOC model using patient-specific human induced pluripotent stem cells (hiPSCs), reprogrammed from the patients blood samples. The chip contains two cell-seeding chambers with flexible silicone pillars to support tissue formation. Healthy and DCM hiPSCs were differentiated into cardiomyocytes, combined with an optimized ratio of human cardiac fibroblasts, encapsulated in a fibrin/Geltrex hydrogel (containing fluorescent beads), and seeded in the device chambers. The tissue gradually compacted and started beating spontaneously. Immunofluorescence assay revealed structural abnormalities in DCM tissues, including reduced cell alignment and elongation. The tissue functional responses (e.g., calcium transients and beating) were investigated after 2 weeks of culture, revealing ventricular tachycardia in DCM tissue and highlighting functional hallmarks of the disease. Finally, the model was validated using a drug with known inotropic and chronotropic effects (i.e., norepinephrine). Our platform demonstrated great potential in drug screening, disease modeling, and personalized medicine.

bioengineering↗

bioRxiv2022

Effective use of genetically-encoded optical biosensors for profiling signalling signatures in iPSC-CMs derived from idiopathic dilated cardiomyopathy patients

Dilated cardiomyopathy (DCM) is a cardiovascular condition that develops when the left ventricle of the heart enlarges, compromising its function and diminishing its capacity to pump oxygenated blood throughout the body. After patients are diagnosed with DCM, disease progression can lead to heart failure and the need for a heart transplantation. DCM is a complex disease where underlying causes can be idiopathic, genetic, or environmental. An incomplete molecular understanding of disease progression poses challenges for drug discovery efforts as effective therapeutics strategies remain elusive. Decades of research using primary cells or animal models have increased our understanding of DCM but has been hampered due to the inaccessibility of human cardiomyocytes, to model cardiac disease, in vitro, in a dish. Here, our goal is to leverage patient-derived hiPSC-CMs and to combine them with biosensors to understand how cellular signalling is altered in DCM. With high sensitivity and versatility, optical biosensors represent the ideal tools to dissect the molecular determinants of cardiovascular disease, in an unbiased manner and in real-time at the level of single cells. By characterizing the pathobiology of dilated cardiomyopathy in a patient-specific manner using high content biosensor-based assays, we aim to uncover personalized mechanisms for the occurrence and development of DCM and as a pathway to development of personalized therapeutics.

biochemistry↗

bioRxiv2020

EEG Alpha Power Predicts the Temporal Sensitivity of Multisensory Integration

Pre-stimulus EEG oscillations, especially in the alpha range (8-13 Hz), can affect the integration of stimulus features into a coherent percept. The effects of alpha power are often explained in terms of alphas inhibitory functions, whereas effects of alpha frequency have bolstered theories of discrete perceptual cycles, where the length of a cycle, or window of integration, is determined by alpha frequency. Such studies typically employ visual detection paradigms with near-threshold or even illusory stimuli. It is unclear whether such results generalize to above-threshold stimuli. Here, we recorded electroencephalography, while measuring temporal discrimination sensitivity in a temporal order judgement task using above-threshold auditory and visual stimuli. We tested whether pre-stimulus oscillations predict audio-visual temporal discrimination sensitivity on a trial-by-trial basis. By applying a jackknife procedure to link single-trial pre-stimulus oscillatory power and instantaneous frequency to psychometric measures, we identified two highly overlapping clusters over posterior sites. One where lower alpha power was associated with higher temporal sensitivity of audiovisual discrimination, and another where higher instantaneous alpha-frequency predicted higher temporal discrimination sensitivity. A follow-up analysis revealed that these effects were not independent, and that the effect of instantaneous frequency could be explained by power modulations in the lower alpha band. These results suggest that temporal sensitivity for above-threshold multisensory stimuli changes spontaneously from moment to moment and is likely related to fluctuations in cortical excitability. Moreover, our results caution against interpreting instantaneous frequency effects as independent from power effects if these effects overlap in time and space.

neuroscience↗

bioRxiv2018

Subjective perceptual experience tracks the neural signature of sensory evidence accumulation during decision formation

How neural representations of low-level visual information are accessed by higher-order processes to inform decisions and give rise to conscious experience is a longstanding question. Research on perceptual decision making has revealed a late event-related EEG potential (the Centro-Parietal Positivity, CPP) to be a correlate of the accumulation of sensory evidence. We tested to what extent this evidence accumulation signal is driven by externally presented (physical) versus internally experienced (subjective) sensory evidence. The results show that the known relationship between external evidence and the evidence accumulation signal (reflected in the CPP amplitude) is mediated by the level of subjective awareness. Additionally, the CPP closely tracks the subjective perceptual evidence during both correct and incorrect trials. Hence, a remarkably close relationship exists between the evidence accumulation process (i.e. CPP) and subjective perceptual experience, suggesting that neural decision processes and components of conscious experience are tightly linked.

neuroscience↗