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The paper reviews and summarizes the historical research that has been carried out in recent decades to explore the connections between esotericism and psychology while highlighting the typical historical and contemporary ways in which psychology and esotericism are linked. This examination underscores why academic research on esotericism is relevant to psychology, including why a substantive definition of esotericism made within the context of psychology is essential. Based on the sources currently at our disposal, it is asserted that the influences of esotericism have never been peripheral to psychology. The foundations and basic features of "esoteric psychology" unfolding within various theoretical frameworks are described. With this paper, the author aims to contribute to the emergence of a critical yet open and flexible discourse that recognizes the impact of esotericism on psychology and is ready to evaluate these influences in an objective way., (© 2024 Wiley Periodicals LLC.)

Infrared neural stimulation has consistently shown that temperature is a critical neuronal state variable. However, a comprehensive understanding of the biophysical background is essential. In this study, using high-density laminar electrode recordings, we investigated the impact of pulsed and continuous-wave infrared illumination on cortical neurons in anesthetized rats ([Formula: see text]). By analyzing the infrared (IR) stimulation-related responses of more than 7500 single units, we found that elevating tissue temperature with IR stimulation resulted in a significant increase in the number of cells affected, including a substantial rise in the number of inhibited cells. Pulsed stimulation affected an average of [Formula: see text] of units, resulting primarily in increased activity. In contrast, continuous stimulation significantly increased the percentage of affected cells to [Formula: see text], with single units tending to be suppressed. Furthermore, when analyzing cell types, a higher percentage of principal cells displayed increased firing rates ([Formula: see text]) compared to suppressed activity ([Formula: see text]). Meanwhile, more interneurons were suppressed ([Formula: see text]) than showed increased activity ([Formula: see text]). On average, the firing rate of neurons reached 90% of the maximal activation within approximately 36 seconds after the onset of infrared stimulation. The proportion of neurons with suppressed activity decreased with cortical depth, while the proportion of neurons with elevated activity increased in deeper layers. These results provide valuable data to understand the mechanism of infrared neural stimulation in the living brain., Competing Interests: Declarations. Conflicts of interests: The authors declare that they have no conflict of interest., (© 2024. The Author(s).)

Traditionally categorized as a uniform sleep phase, rapid eye movement sleep exhibits substantial heterogeneity with its phasic and tonic constituents showing marked differences regarding many characteristics. Here, we investigate how tonic and phasic states differ with respect to aperiodic neural activity, a marker of arousal and sleep. Rapid eye movement sleep heterogeneity was assessed using either binary phasic-tonic (n = 97) or continuous (in 60/97 participants) approach. Slopes of the aperiodic power component were measured in the low (2-30 Hz, n = 97) and high (30-48 Hz, n = 60/97) frequency bands with the Irregularly Resampled Auto-Spectral Analysis applied on electroencephalography. Rapid eye movement amplitudes were quantified with the YASA applied on electrooculography (n = 60/97). The binary approach revealed that the phasic state is characterized by steeper low-band slopes with small effect sizes and some topographical heterogeneity over datasets. High-band aperiodic slopes were flatter in the phasic versus tonic state with medium-to-large effect sizes over all areas in both datasets. The continuous approach confirmed these findings. The temporal analysis within rapid eye movement episodes revealed that aperiodic activity preceding or following EM events did not cross-correlate with eye movement amplitudes. This study demonstrates that aperiodic slopes can serve as a reliable marker able to differentiate between phasic and tonic constituents of rapid eye movement sleep and reflect phasic rapid eye movement event intensity. However, rapid eye movement events could not be predicted by preceding aperiodic activity and vice versa, at least not with scalp electroencephalography., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Finding optimal parameters for detailed neuronal models is a ubiquitous challenge in neuroscientific research. In recent years, manual model tuning has been gradually replaced by automated parameter search using a variety of different tools and methods. However, using most of these software tools and choosing the most appropriate algorithm for a given optimization task require substantial technical expertise, which prevents the majority of researchers from using these methods effectively. To address these issues, we developed a generic platform (called Neuroptimus) that allows users to set up neural parameter optimization tasks via a graphical interface, and to solve these tasks using a wide selection of state-of-the-art parameter search methods implemented by five different Python packages. Neuroptimus also offers several features to support more advanced usage, including the ability to run most algorithms in parallel, which allows it to take advantage of high-performance computing architectures. We used the common interface provided by Neuroptimus to conduct a detailed comparison of more than twenty different algorithms (and implementations) on six distinct benchmarks that represent typical scenarios in neuronal parameter search. We quantified the performance of the algorithms in terms of the best solutions found and in terms of convergence speed. We identified several algorithms, including covariance matrix adaptation evolution strategy and particle swarm optimization, that consistently, without any fine-tuning, found good solutions in all of our use cases. By contrast, some other algorithms including all local search methods provided good solutions only for the simplest use cases, and failed completely on more complex problems. We also demonstrate the versatility of Neuroptimus by applying it to an additional use case that involves tuning the parameters of a subcellular model of biochemical pathways. Finally, we created an online database that allows uploading, querying and analyzing the results of optimization runs performed by Neuroptimus, which enables all researchers to update and extend the current benchmarking study. The tools and analysis we provide should aid members of the neuroscience community to apply parameter search methods more effectively in their research., Competing Interests: The authors declare that no competing interests exist., (Copyright: © 2024 Mohácsi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/Objectives : Accurately classifying Electroencephalography (EEG) signals is essential for the effective operation of Brain-Computer Interfaces (BCI), which is needed for reliable neurorehabilitation applications. However, many factors in the processing pipeline can influence classification performance. The objective of this study is to assess the effects of different processing steps on classification accuracy in EEG-based BCI systems. Methods : This study explores the impact of various processing techniques and stages, including the FASTER algorithm for artifact rejection (AR), frequency filtering, transfer learning, and cropped training. The Physionet dataset, consisting of four motor imagery classes, was used as input due to its relatively large number of subjects. The raw EEG was tested with EEGNet and Shallow ConvNet. To examine the impact of adding a spatial dimension to the input data, we also used the Multi-branch Conv3D Net and developed two new models, Conv2D Net and Conv3D Net. Results : Our analysis showed that classification accuracy can be affected by many factors at every stage. Applying the AR method, for instance, can either enhance or degrade classification performance, depending on the subject and the specific network architecture. Transfer learning was effective in improving the performance of all networks for both raw and artifact-rejected data. However, the improvement in classification accuracy for artifact-rejected data was less pronounced compared to unfiltered data, resulting in reduced precision. For instance, the best classifier achieved 46.1% accuracy on unfiltered data, which increased to 63.5% with transfer learning. In the filtered case, accuracy rose from 45.5% to only 55.9% when transfer learning was applied. An unexpected outcome regarding frequency filtering was observed: networks demonstrated better classification performance when focusing on lower-frequency components. Higher frequency ranges were more discriminative for EEGNet and Shallow ConvNet, but only when cropped training was applied. Conclusions : The findings of this study highlight the complex interaction between processing techniques and neural network performance, emphasizing the necessity for customized processing approaches tailored to specific subjects and network architectures.

The aim of this work is to incorporate lanthanide-cored upconversion nanoparticles (UCNP) into the surface of microengineered biomedical implants to create a spatially controlled and optically releasable model drug delivery device in an integrated fashion. Our approach enables silicone-based microelectrocorticography (ECoG) implants holding platinum/iridium recording sites to serve as a stable host of UCNPs. Nanoparticles excitable in the near-infrared (lower energy) regime and emitting visible (higher energy) light are utilized in a study. With the upconverted higher energy photons, we demonstrate the induction of photochemical (cleaving) reactions that enable the local release of specific dyes as a model system near the implant. The modified ECoG electrodes can be implanted in brain tissue to act as an uncaging system that releases small amounts of substance while simultaneously measuring the evoked neural response upon light activation. In this paper, several technological challenges like the surface modification of UCNPs, the immobilization of particles on the implantable platform, and measuring the stability of integrated UCNPs in in vitro and in vivo conditions are addressed in detail. Besides the chemical, mechanical, and optical characterization of the ready-to-use devices, the effect of nanoparticles on the original electrophysiological function is also evaluated. The results confirm that silicone-based brain-machine interfaces can be efficiently complemented with UCNPs to facilitate local model drug release.

Due to technical roadblocks, it is unclear how visual circuits represent multiple features or how behaviorally relevant representations are selected for long-term memory. Here we developed Moculus, a head-mounted virtual reality platform for mice that covers the entire visual field, and allows binocular depth perception and full visual immersion. This controllable environment, with three-dimensional (3D) corridors and 3D objects, in combination with 3D acousto-optical imaging, affords rapid visual learning and the uncovering of circuit substrates in one measurement session. Both the control and reinforcement-associated visual cue coding neuronal assemblies are transiently expanded by reinforcement feedback to near-saturation levels. This increases computational capability and allows competition among assemblies that encode behaviorally relevant information. The coding assemblies form partially orthogonal and overlapping clusters centered around hub cells with higher and earlier ramp-like responses, as well as locally increased functional connectivity., Competing Interests: Competing interests: G.D., B.R. and G.S. are inventors on patent PCT/HU2020/050029. B.R. is a founder of Femtonics and a member of its scientific advisory board. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Objective: Phonocardiography has recently gained popularity in low-cost and remote monitoring, including passive fetal heart monitoring. The development of methods which analyse phonocardiographic data tries to capitalize on this opportunity, and in recent years a multitude of such algorithms and models have been published. In these approaches there is little to no standardization and multiple parts of these models have to be reimplemented on a case-by-case basis. Datasets containing heart sound recordings also lack standardization in both data storage and labeling, especially in fetal phonocardiography., Approach: We are presenting a toolbox that can serve as a basis for a future standard framework for heart sound analysis. This toolbox contains some of the most widely used processing steps and with these, complex analysis pipelines can be created. These functions can be tested individually., Main Results: Due to the interdependence of the steps, we validated the current segmentation stage using two phonocardiogram datasets, a fetal dataset comprising 50 one-minute abdominal PCG recordings, which include 6758 S1 and 6729 S2 labels and a filtered version of the dataset used in the 2022 PhysioNet Challenge, containing 413 records with 9795 S1 and 9761 S2 labels. Our results were compared to other common and publicly available segmentation methods, such as peak detection with the Neurokit2 library, and the Hidden Semi-Markov Model by Springer et al. Our best model achieved a 96.1% F1 score and 11.7 ms mean absolute error for fetal S1 detection, and 81.3% F1 score and 50.5 ms mean absolute error for PhysioNet S1 detection., Significance: Our detection method outperformed all other tested methods on the fetal dataset and
achieved results comparable to the state of the art on the PhysioNet dataset. Accurate segmentation of signals is critical for the calculation of accurate statistical measures and the creation of classification models. Our toolbox contains functions for both feature extraction and calculation of statistics which are compatible with the previous steps. All of our methods can be fine tuned for specific datasets. pyPCG is available on https://pypcg-toolbox.readthedocs.io/en/latest/., (Creative Commons Attribution license.)

Azimuthal orientation and handedness dependence of the optical responses, accompanied by asymmetric transmission and asymmetric dichroism, were demonstrated on multilayers constructed with subwavelength periodic arrays of Babinet complementary miniarrays, illuminated by linearly and circularly polarized light. In case of single-sided illumination asymmetric optical responses were observed at the spectral location of maximal cross-polarization that is accompanied by radiative electric dipoles and weak, slowly-rotating in-plane magnetic dipoles on the nano-objects; where the outgoing waves are elliptically (almost circularly) polarized. The negative index material phenomenon was demonstrated, where the electric and magnetic dipoles overlap both spatially and spectrally. The negative index material (NIM) phenomenon is accompanied by electric multipoles that add up non-radiatively and correlates with the strong, pronouncedly-tilted, rotating magnetic dipoles characteristic on the nano-entities, where the outgoing waves are linearly (slightly elliptically) polarized. By illuminating the multilayer with two counter-propagating circularly polarized beams it was proven that asymmetrical normal component displacement currents at the bounding interfaces, arising along flat and tilted bands, accompany the asymmetric copolarized and cross-polarized transmission. The latter correlates with the asymmetric dichroism in the cross-polarized signal observed in case of single-sided circularly polarized light illumination. The dispersion maps in the single-sided asymmetrical co-polarized reflectance and absorptance indicate flat bands of analogous and complementary extrema, proving the partially dichroic nature of the observed asymmetric phenomena. The Tellegen (chirality) coefficients exhibit a maximum in a spectral region coincident with the asymmetric transmission (maximal polarization rotation in the 90° azimuthal orientation). The multilayer is proposed as an ultrathin NIM and nonreciprocal nanophotonic element., Competing Interests: Declarations. Competing interests: The authors declare no conflicts of interest regarding this article., (© 2024. The Author(s).)

Background: Advanced-stage non-small cell lung cancer (NSCLC) poses treatment challenges, with immune checkpoint inhibitors (ICIs) as the main therapy. Emerging evidence suggests the gut microbiome significantly influences ICI efficacy. This study explores the link between the gut microbiome and ICI outcomes in NSCLC patients, using metatranscriptomic (MTR) signatures., Methods: We utilized a de novo assembly-based MTR analysis on fecal samples from 29 NSCLC patients undergoing ICI therapy, segmented according to progression-free survival (PFS) into long (> 6 months) and short (≤ 6 months) PFS groups. Through RNA sequencing, we employed the Trinity pipeline for assembly, MMSeqs2 for taxonomic classification, DESeq2 for differential expression (DE) analysis. We constructed Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost) machine learning (ML) algorithms and comprehensive microbial profiles., Results: We detected no significant differences concerning alpha-diversity, but we revealed a biologically relevant separation between the two patient groups in beta-diversity. Actinomycetota was significantly overrepresented in patients with short PFS (vs long PFS, 36.7% vs. 5.4%, p < 0.001), as was Euryarchaeota (1.3% vs. 0.002%, p = 0.009), while Bacillota showed higher prevalence in the long PFS group (66.2% vs. 42.3%, p = 0.007), when comparing the abundance of corresponding RNA reads. Among the 120 significant DEGs identified, cluster analysis clearly separated a large set of genes more active in patients with short PFS and a smaller set of genes more active in long PFS patients. Protein Domain Families (PFAMs) were analyzed to identify pathways enriched in patient groups. Pathways related to DNA synthesis and Translesion were more enriched in short PFS patients, while metabolism-related pathways were more enriched in long PFS patients. E. coli-derived PFAMs dominated in patients with long PFS. RF, SVM and XGBoost ML models all confirmed the predictive power of our selected RNA-based microbial signature, with ROC AUCs all greater than 0.84. Multivariate Cox regression tested with clinical confounders PD-L1 expression and chemotherapy history underscored the influence of n = 6 key RNA biomarkers on PFS., Conclusion: According to ML models specific gut microbiome MTR signatures' associate with ICI treated NSCLC outcomes. Specific gene clusters and taxa MTR gene expression might differentiate long vs short PFS., Competing Interests: Declarations Ethics approval and consent to participate In the current study, we adhered to the Helsinki Declaration’s study criteria established by the World Medical Association. The study was formally approved by the national ethics committee, specifically the Hungarian Scientific and Research Ethics Committee of the Medical Research Council (ETTTUKEB- 50302-2/2017/EKU). Participation in the study was contingent upon the provision of permission by all patients involved. To maintain confidentiality, patient IDs were removed after the collection of clinicopathological data, thereby preventing direct or indirect identification of patients. Consent for publication All authors agree to submit the article for publication. Competing interests The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

A positive association between pubertal maturity as assessed by skeletal development, and specific cognitive abilities has recently been demonstrated in a cohort of adolescent girls. The current study explores the impact of chronological age and relative pubertal maturity on executive function within the same cohort. Relative maturity, determined by the difference between chronological age and skeletal age, establishes the criteria for enrolling participants into average, advanced, or delayed relative maturity subgroups. Performance is assessed using the Numerical Stroop test and analyzed across four conditions, each with varying task requirements related to inhibition and task switching. The effects of chronological age and relative maturity on executive functions are tested by a linear mixed model. Within the examined age-range (12-15 y), a more protracted development was found for inhibition as compared to switching. In line with the previous findings, the results reveal significant development in executive performance as a function of chronological age, and relative maturity also demonstrated significant effect on the development of executing functioning. The significant interaction effect between Chronological Age and Relative Maturity suggests that the degree of interplay between these factors varies across the examined age range. Specifically, relative maturity may have a more noticeable impact on EF functioning in middle adolescence compared to early adolescence., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

While the majority of proteins with available structures are able to fold independently and mediate interactions only after acquiring their folded state, a subset of the known protein complexes contains protein chains that are intrinsically disordered in isolation. The Mutual Folding Induced by Binding (MFIB) database collects and classifies protein complexes, wherein all constituent protein chains would be unstable/disordered in isolation but fold into a well-defined 3D complex structure upon binding. This phenomenon is often termed as cooperative folding and binding or mutual synergistic folding (MSF). Here we present a major update to the database: we collected and annotated hundreds of new protein complexes fulfilling the criteria of MSF, leading to an almost six-fold increase in the size of the database. Many novel features have also been introduced, such as clustering of the complexes based on structural similarity and domain types, assigning different evidence levels to each entry and adding the evidence coverage label that allowed us to include complexes of multi(sub)domain monomers with partial MSF. The MFIB 2.0 database is available at https://mfib.pbrg.hu., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Introduction: Intestinal ischemia/reperfusion (I/R) injury is associated with high mortality and there is an unmet need for novel therapies. The intestinal expression of cyclooxygenase-2 (COX-2) increases rapidly after mesenteric I/R, but it is still a question of debate whether selective COX-2 inhibitors can mitigate I/R-induced gut injury. Here we aimed to compare the effect of celecoxib and rofecoxib, two selective COX-2 inhibitors, on intestinal I/R-induced injury in rats., Methods: Wistar rats were treated with celecoxib (10 and 100 mg/kg), rofecoxib (5 and 50 mg/kg), or vehicle for 8 days via gavage and then were subjected to sham operation or mesenteric I/R. Small intestinal inflammation and tissue damage were assessed by histology and quantification of inflammatory and tight junction proteins. The intestinal activity of COX enzymes was determined by a COX activity assay., Results: The higher dose of celecoxib reduced the I/R-associated increase in inflammatory mediators (myeloperoxidase, pentraxin 3, COX-2, interleukin-1β) and loss of tight junction proteins (claudin-1, occludin), whereas the lower dose of celecoxib was only marginally effective. However, even high-dose celecoxib failed to prevent the histological injury of the mucosa. In contrast to celecoxib, rofecoxib did not affect intestinal inflammation and injury at any of the tested doses. Neither celecoxib nor rofecoxib affected the I/R-induced changes of HO-1 and PPAR-γ, known off-targets of COX-inhibitors, but celecoxib increased the I/R-induced elevation of Bax/Bcl-2, a marker of apoptosis, whereas rofecoxib reduced the elevation of phospho-Akt. Importantly, high-dose celecoxib, but not rofecoxib, has already reduced intestinal COX-1 activity., Conclusion: Our study provides evidence for the higher anti-inflammatory efficacy of celecoxib compared to rofecoxib in mesenteric I/R injury, which is likely due to its lower selectivity for COX-2. However, even high-dose celecoxib was unable to reduce the mucosal damage. Our results suggest that selective COX-2 inhibitors have only limited therapeutic value in intestinal I/R injury., Competing Interests: Author BH is currently employed by Gedeon Richter Plc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 László, Hutka, Tóth, Hegyes, Demeter, Haghighi, Wachtl, Kelemen, Jakab, Gyires and Zádori.)

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to integrate information obtained from diverse experimental approaches. To address this challenge, we present a community-based, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to potentially address a range of scientific questions. In this article, we describe the methods used to set up simulations to reproduce in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce experimental findings. Finally, we make data, code, and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This community-based model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Romani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The popularity of video games has considerably increased in recent years, with approximately 3.24 billion players worldwide in 2021. Empirical evidence suggests that the quality of engagement in video games can determine whether a gaming activity is associated with psychological distress (i.e., problematic gaming) or self-enhancing outcomes (i.e., esports career pursuits). This study investigates the role of influential gaming role models and other external factors relating to fame appeal in gamers' different ways of engagement., Methods: A total of 803 adolescent and adult gamers (89.29 % male, Mage = 24.90 years, SD = 6.13) were recruited through an online questionnaire., Results: A path analysis was constructed demonstrating that wishful identification partially mediated the relationship between desire for fame and esports career planning. Moreover, maladaptive daydreaming fully mediated the association between desire for fame and gaming disorder symptoms. Wishful identification with gaming role models predicted both esports career planning and gaming disorder symptoms., Conclusions: The findings shed light on the importance of considering the role of gaming role models in predicting healthy and problematic gaming patterns., Competing Interests: Declaration of competing interest The authors declare no conflict of interest. The datasets analyzed in the current study are available from the corresponding author upon request., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Although otitis media with effusion (OME) is a common cause of hearing impairment in children, little is known about its microbiological background. We aimed to analyse the microbiome of the middle ear fluid (MEF) in OME to identify microbiological, demographic and environmental factors that may potentially influence the middle ear microbiome. In addition, we aimed to compare the results of conventional culture techniques and PCR-based methods., Methods: 39 samples from children with OME were investigated using conventional culture and 16S rRNA sequencing. Bioinformatic analyses were carried out to assess the microbial communities and their association with clinical data., Results: By conventional culture technique bacteria could be cultured in 33 % of the MEF samples; the most frequent bacterium was Haemophilus influenzae , followed by Staphylococcus species, Cutibacterium acne , and Streptococcus species. The 16S rRNA analysis showed that Alloiococcus was the most abundant bacterium, followed by Haemophilus , Streptococcus . and Sphingobium .A "High Alloiococcus group" with significantly lower and a "Low Alloiococcus group" with significantly higher alpha and beta diversity could be defined. Children born by Caesarean sections had lower beta and Shannon diversity than patients born by natural birth. Breastfeeding for at least six months showed a negative correlation with alpha diversity. Age, previous antibiotic treatment, parental smoking, duration of symptoms, existence of siblings, did not alter the significantly bacterial composition of MEF samples and there were no significant differences in regard to alpha or beta diversity., Conclusion: The conventional culture technique and 16S rRNA results were not congruent. Remarkably, Alloiococcus could not be cultured at all, even by 16S rRNA analysis the presence of Alloiococcus seems to be important. Based on our results, A. otitidis possibly impacts the diversity of middle ear microbiome in children with OME. However, further studies are required to determine the role of A. otidis in middle ear pathologies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dora Szabo reports financial support was provided by 10.13039/100020916Hungarian Research Network. Dora Szabo reports financial support was provided by Horizon Europe. Dora Szabo reports a relationship with 10.13039/100020916Hungarian Research Network that includes: funding grants. Dora Szabo reports a relationship with Horizon Europe that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

The hippocampus has a crucial role in the formation, consolidation and recall of memories as well as in navigation related processes. These functions are in the focus of neuroscience and different disciplines have contributed to this research field for decades. Two-photon imaging in awake animals is a valuable new aspect for these observations, especially when it is supported by electrophysiology. In this study, we applied high speed two-photon hippocampal imaging through a chronically implanted, soft, transparent microelectrode (STM) device incorporated into a cranial window chamber in awake mice. We monitored the impedance of the recording sites over the course of the experiments to observe long-term changes in recording quality. The large-scale ipsilateral local field potential (LFP) recordings from the dorsal hippocampus provided reliable sharp wave-ripples (SPW-Rs), multi-unit activity (MUA) and single-unit activity (SUA) for up to two months. Calcium imaging of GCaMP6f. labeled cells from the CA1 pyramidal layer under the transparent device was possible even after six months in thy1-GCaMP6f. transgenic mice. We investigated the immune response with GFAP staining after the end of the long-term experiments. Based on our results, this dedicated transparent electrode device proved to be suitable for simultaneous two-photon imaging and large-scale electrophysiological measurements in chronic experiments in mice., (© 2024. The Author(s).)

Mechanotransduction, the process of how cells sense and convert mechanical stimuli into biochemical response, is crucial in the migration of leukocytes or cancer cells through the endothelium during inflammation or metastasis. Migrating cells exert forces on the endothelium through cell surface adhesion molecules, such as platelet endothelial adhesion molecule PECAM-1, and this is essential for a successful transmigration. To study PECAM-1-mediated mechanotransduction, we applied PECAM-1-antibody-coated magnetic beads and exerted about 40 pN force on the endothelial monolayer. We show that force increases cell-ECM adhesion in the cell center and is accompanied by the opening of cell-cell junctions. Upon depletion of the MEK/ERK kinase, BRAF force increases cell-ECM adhesion both at the cell periphery and in the cell center, but this does not result in the opening of cell-cell junctions. Decreasing cell-ECM adhesion in BRAF-depleted cells through FAK inhibition results in the remodeling of cell-cell junctions. Force-induced increase in cell-ECM adhesion in the cell center correlates with the activation of the transcriptional cofactor Yes-associated protein (YAP). Furthermore, the induced activation of YAP through LATS inhibition prevents junctional remodeling in control cells. Thus, the activation of YAP might determine the strength of cell-cell junctions during PECAM-1-mediated mechanotransduction.

The advancements in targeted drug release and experimental neuroscience have amplified the scientific interest in photolabile protecting groups (PPGs) and photouncaging. The growing need for the detection of uncaging events has led to the development of reporters with fluorescence turn-on upon uncaging. In contrast, fluorescent tags with turn-off properties have been drastically underexplored, although there are applications where they would be sought after. In this work, a rhodamine-based fluorescent tag is developed with signal turn-off following photouncaging. One-photon photolysis experiments reveal a ready loss of red fluorescence signal upon UV (365 nm) irradiation, while no significant change is observed in control experiments in the absence of PPG or with irradiation around the absorption maximum of the fluorophore (595 nm). The two-photon photolysis of the turn-off fluorescent tag is explored in hydrogel photolithography experiments. The hydrogel-bound tag enables the power-, dwell time-, and wavelength-dependent construction of intricate patterns and gradients. Finally, a prominent caged neurotransmitter (MNI-Glu) is modified with the fluorescent tag, resulting in the glutamate precursor named as GlutaTrace with fluorescence traceability and turn-off upon photouncaging. GlutaTrace is successfully applied for the visualization of glutamate precursor distribution following capillary microinjection and for the selective excitation of neurons in a mouse brain model.