Cardiomyocyte engineering: The meeting point of transcription factors, signaling networks, metabolism and function.

Direct cardiac reprogramming or transdifferentiation is a relatively new and promising area in regenerative therapy, cardiovascular disease modeling, and drug discovery. Effective reprogramming of fibroblasts is limited by their plasticity, that is, their ability to reprogram, and depends on solving several levels of tasks: inducing cardiomyocyte-like cells and obtaining functionally and metabolically mature cardiomyocytes. Currently, in addition to the use of more classical approaches such as overexpression of exogenous transcription factors, activation of endogenous cardiac transcription factors via controlled nucleases, such as CRISPR, represents another interesting way to obtain cardiomyocytes.

A Case Study on EEG Signal Correlation Towards Potential Epileptic Foci Triangulation.

The precise localization of epileptic foci with the help of EEG or iEEG signals is still a clinical challenge with current methodology, especially if the foci are not close to individual electrodes. On the research side, dipole reconstruction for focus localization is a topic of recent and current developments. Relatively low numbers of recording electrodes cause ill-posed and ill-conditioned problems in the inversion of lead-field matrices to calculate the focus location.

Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the HS/AKT/GSK3β signaling axis.

Pyridoxal-5-phosphate (PLP) enhances the synthesis of endogenous hydrogen sulfide, a potent regulator of cell metabolism. We used 24-month-old rats to investigate the PLP mitoprotective function in the aging heart. We demonstrated improvement of mitochondrial bioenergetic functions, inhibition of mPTP opening after PLP administration.

Information sharing within a social network is key to behavioral flexibility-Lessons from mice tested under seminaturalistic conditions.

Being part of a social structure offers chances for social learning vital for survival and reproduction. Nevertheless, studying the neural mechanisms of social learning under laboratory conditions remains challenging. To investigate the impact of socially transmitted information about rewards on individual behavior, we used Eco-HAB, an automated system monitoring the voluntary behavior of group-housed mice under seminaturalistic conditions.

Neural processing of sad and happy autobiographical memories in women with depression and borderline personality disorder.

Patients with major depressive disorder (MDD) and borderline personality disorder (BPD) are reported to have disrupted autobiographical memory (AM). Using functional magnetic resonance imaging we investigated behavioral and neural processing of the recall of emotional (sad and happy) memories in 30 MDD, 18 BPD, and 34 healthy control (HC) unmedicated women. The behavioral results showed that the MDD group experienced more sadness than the HC after the sad recall, while BPD participants experienced less happiness than HC after the happy recall.

Motile Cilia in Female and Male Reproductive Tracts and Fertility.

Motile cilia are evolutionarily conserved organelles. In humans, multiciliated cells (MCCs), assembling several hundred motile cilia on their apical surface, are components of the monolayer epithelia lining lower and upper airways, brain ventricles, and parts of the reproductive tracts, the fallopian tube and uterus in females, and efferent ductules in males. The coordinated beating of cilia generates a force that enables a shift of the tubular fluid, particles, or cells along the surface of the ciliated epithelia.

Structure of the ciliary tip central pair reveals the unique role of the microtubule-seam binding protein SPEF1.

Motile cilia are unique organelles with the ability to autonomously move. Force generated by beating cilia propels cells and moves fluids. The ciliary skeleton is made of peripheral doublet microtubules and a central pair (CP) with a distinct structure at the tip.

Unveiling the neural dynamics of the theory of mind: a fMRI study on belief processing phases.

Theory of mind (ToM), the ability to interpret others' behaviors in terms of mental states, has been extensively studied through the False-Belief Task (FBT). However, limited research exists regarding the distinction between different phases of FBT, suggesting that they are subserved by separate neural mechanisms. Further inquiry into this matter seems crucial for deepening our knowledge of the neurocognitive basis of mental-state processing.

Antithrombotic but not anticoagulant activity of the thrombin-binding RNA aptamer Apta-1.

Background And Purpose: Pharmacological intervention of thrombosis is challenging, requiring a fined tune balance between beneficial antithrombotic effect versus risk of major bleeding complications. In this investigation, we elucidated the antithrombotic capacity of the novel 90-mer RNA aptamer Apta-1 and its underlying mechanism of action.

Experimental Approach: We utilized three independent in vivo animal models to establish antithrombotic activity and bleeding risk of Apta-1.

How does teaching experience impact brain processes underlying the theory of mind? Study on primary school educators.

Despite its importance for daily social interactions, few studies have explored interindividual differences in the Theory of Mind (ToM) abilities of healthy adults. We used Children's False-Attribution (CFA), Children's False-Beliefs (CFB), and Belief-Desire Reasoning tasks, along with fMRI-based assessments, in a comparative analysis of ToM among primary school teachers (PST;  = 27), skilled in social interactions with children, and matched controls (MC;  = 24), who lacked such experience. PST demonstrated slower reaction times than MC in Adult and Child false-belief stories of CFB.

Proteomics analysis in rats reveals convergent mechanisms between major depressive disorder and dietary zinc deficiency.

Background: Preclinical and clinical studies have shown that dietary zinc deficiency can lead to symptoms similar to those observed in major depressive disorder (MDD). However, the underlying molecular mechanisms remain unclear. To investigate these mechanisms, we examined proteomic changes in the prefrontal cortex (PFC) and hippocampus (HP) of rats, two critical brain regions implicated in the pathophysiology of depression.

High-throughput formulation of reproducible 3D cancer microenvironments for drug testing in myeloid leukemia.

Leukemic microenvironment has been recognized as a factor that strongly supports the mechanisms of resistance. Therefore, targeting the microenvironment is currently one of the major directions in drug development and preclinical studies in leukemia. Despite the variety of available leukemia 3D culture models, the reproducible generation of miniaturized leukemic microenvironments, suitable for high-throughput drug testing, has remained a challenge.

Deciphering the peculiarities of cell types in the septum.

Similar to other brain regions, the neurons in the lateral septum (LS) are of heterogeneous populations. However, their resting membrane potential (RMP) on average is not too far apart. Cells were characterized based on biological markers by using brain slices, as under these in vitro conditions, neurons retain their morphologies.

Processing of self-related thoughts in experienced users of classic psychedelics: A source localisation EEG study.

Background: Psychedelics have gained increasing interest in scientific research due to their ability to induce profound alterations in perception, emotional processing and self-consciousness. However, the research regarding the functioning of individuals who use psychedelics in naturalistic contexts remains limited.

Aims: Here we aim to explore psychological and neurophysiological differences between naturalistic psychedelics users and non-users in terms of processing of self-related thoughts.

Remodeling of Il4-Il13-Il5 locus underlies selective gene expression.

The type 2 cytokines, interleukin (IL)-4, IL-13 and IL-5 reside within a multigene cluster. Both innate (ILC2) and adaptive T helper 2 (T2) lymphocytes secrete type 2 cytokines with diverse production spectra. Using transcription factor footprint and chromatin accessibility, we systemically cataloged regulatory elements (REs) denoted as SHS-I/II, KHS-I/II, +6.

NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.

Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex.

The Relation Between Mitochondrial Membrane Potential and Reactive Oxygen Species Formation.

Mitochondria are considered one of the main sites of reactive oxygen species (ROS) production in the eukaryotic cells. For this reason, mitochondrial dysfunction associated with increased ROS production underlies various pathological conditions as well as promotes aging. Chronically increased rates of ROS production contribute to oxidative damage to macromolecules, i.

Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses.

Stress resilience is the ability of neuronal networks to maintain their function despite the stress exposure. Using a mouse model we investigate stress resilience phenomenon. To assess the resilient and anhedonic behavioral phenotypes developed after the induction of chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods.

Performance of game sessions in VR vs standard 2D monitor environment. an EEG study.

Nowadays studies using Virtual Reality (VR) are gaining high popularity due to VR being a better approximation of the ecological environment for visual experiments than standard 2D display settings. VR technology has been already applied in medicine in the therapy of mental disorders, neurorehabilitation, and neurofeedback. However, its effectiveness compared to the standard 2D procedure is still not fully documented and limited information about the neurophysiological underpinnings of VR is provided.

Molecular analysis of inherited disorders of cornification in polish patients show novel variants and functional data and provokes questions on the significance of secondary findings.

Background: The Mendelian Disorders of Cornification (MeDOC) comprise a large number of disorders that present with either localised (palmoplantar keratoderma, PPK) or generalised (ichthyoses) signs. The MeDOC are highly heterogenic in terms of genetics and phenotype. Consequently, diagnostic process is challenging and before implementation of the next generation sequencing, was mostly symptomatic, not causal, which limited research on those diseases.