Quantitative comparison of a mobile, tablet-based eye-tracker and two stationary, video-based eye-trackers.

The analysis of eye movements is a noninvasive, reliable and fast method to detect and quantify brain (dys)function. Here, we investigated the performance of two novel eye-trackers-the Thomas Oculus Motus-research mobile (TOM-rm) and the TOM-research stationary (TOM-rs)-and compared them with the performance of a well-established video-based eye-tracker, i.e.

Standardized wireless deep brain stimulation system for mice.

Deep brain stimulation (DBS) has emerged as a revolutionary technique for accessing and modulating brain circuits. DBS is used to treat dysfunctional neuronal circuits in neurological and psychiatric disorders. Despite over two decades of clinical application, the fundamental mechanisms underlying DBS are still not well understood.

Chamber-specific contractile responses of atrial and ventricular hiPSC-cardiomyocytes to GPCR and ion channel targeting compounds: A microphysiological system for cardiac drug development.

Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) have found utility for conducting in vitro drug screening and disease modelling to gain crucial insights into pharmacology or disease phenotype. However, diseases such as atrial fibrillation, affecting >33 M people worldwide, demonstrate the need for cardiac subtype-specific cells. Here, we sought to investigate the base characteristics and pharmacological differences between commercially available chamber-specific atrial or ventricular hiPSC-CMs seeded onto ultra-thin, flexible PDMS membranes to simultaneously measure contractility in a 96 multi-well format.

Using camera-guided electrode microdrive navigation for precise 3D targeting of macaque brain sites.

Spatial accuracy in electrophysiological investigations is paramount, as precise localization and reliable access to specific brain regions help the advancement of our understanding of the brain's complex neural activity. Here, we introduce a novel, multi camera-based, frameless neuronavigation technique for precise, 3-dimensional electrode positioning in awake monkeys. The investigation of neural functions in awake primates often requires stable access to the brain with thin and delicate recording electrodes.

Neuroplastin splice variants Np55 and Np65: Who is doing the job in macrophages?

Neuroplastin, a paralog of CD147/Basigin, is known as a neuronal cell adhesion molecule and as an auxiliary subunit of plasma membrane calcium ATPases in both neurons and adaptive immune cells. Recently, an interesting study by Ren et al. (2022) provided evidence for an important role of neuroplastin in macrophages during bacterial infection.

Drosophila Atlastin regulates synaptic vesicle mobilization independent of bone morphogenetic protein signaling.

Background: The endoplasmic reticulum (ER) contacts endosomes in all parts of a motor neuron, including the axon and presynaptic terminal, to move structural proteins, proteins that send signals, and lipids over long distances. Atlastin (Atl), a large GTPase, is required for membrane fusion and the structural dynamics of the ER tubules. Atl mutations are the second most common cause of Hereditary Spastic Paraplegia (HSP), which causes spasticity in both sexes' lower extremities.

Interactive nanocluster compaction of the ELKS scaffold and Cacophony Ca channels drives sustained active zone potentiation.

At presynaptic active zones (AZs), conserved scaffold protein architectures control synaptic vesicle (SV) release by defining the nanoscale distribution and density of voltage-gated Ca channels (VGCCs). While AZs can potentiate SV release in the minutes range, we lack an understanding of how AZ scaffold components and VGCCs engage into potentiation. We here establish dynamic, intravital single-molecule imaging of endogenously tagged proteins at AZs undergoing presynaptic homeostatic potentiation.

Ca Homeostasis by Plasma Membrane Ca ATPase (PMCA) 1 Is Essential for the Development of DP Thymocytes.

The strength of Ca signaling is a hallmark of T cell activation, yet the role of Ca homeostasis in developing T cells before expressing a mature T cell receptor is poorly understood. We aimed to unveil specific functions of the two plasma membrane Ca ATPases expressed in T cells, PMCA1 and PMCA4. On a transcriptional and protein level we found that PMCA4 was expressed at low levels in CD4CD8 double negative (DN) thymocytes and was even downregulated in subsequent stages while PMCA1 was present throughout development and upregulated in CD4CD8 double positive (DP) thymocytes.

Hybrid Cell Analysis System to Assess Structural and Contractile Changes of Human iPSC-Derived Cardiomyocytes for Preclinical Cardiac Risk Evaluation.

Cardiac contractility assessment is of immense importance for the development of new therapeutics and their safe transition into clinical stages. While human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold promise to serve as a human-relevant model in preclinical phases of drug discovery and safety pharmacology, their maturity is still controversial in the scientific community and under constant development. We present a hybrid contractility and impedance/extracellular field potential (EFP) technology, adding significant pro-maturation features to an industry-standard 96-well platform.

Lateralization in hemi-parkinsonian rats is affected by deep brain stimulation or glutamatergic neurotransmission in the inferior colliculus.

After unilateral lesion of the medial forebrain bundle (MFB) by 6-OHDA rats exhibit lateralized deficits in spontaneous behavior or apomorphine-induced rotations. We investigated whether such lateralization is attenuated by either deep brain stimulation (DBS) or glutamatergic neurotransmission in the inferior colliculus (IC) of Wistar rats. Intracollicular DBS did not affect spontaneous lateralization but attenuated apomorphine-induced rotations.

Prevalence of overweight and obesity among school children in Mysuru, Karnataka.

Unlabelled: Childhood obesity has become a major public health challenge in developing countries including India due to the changes in the lifestyle and food habits of children owing to the influence of urban culture and technological growth. The present study is a cross-sectional, school-based study conducted to assess the prevalence of obesity and to determine the demographic variables influencing the obesity among school children.

Methods: The study included 440 students (Boys: 240, Girls: 200) from two randomly selected schools of Mysuru city, Karnataka.

Separation of presynaptic Ca2 and Ca1 channel function in synaptic vesicle exo- and endocytosis by the membrane anchored Ca pump PMCA.

Synaptic vesicle (SV) release, recycling, and plastic changes of release probability co-occur side by side within nerve terminals and rely on local Ca signals with different temporal and spatial profiles. The mechanisms that guarantee separate regulation of these vital presynaptic functions during action potential (AP)-triggered presynaptic Ca entry remain unclear. Combining genetics with electrophysiology and imaging reveals the localization of two different voltage-gated calcium channels at the presynaptic terminals of glutamatergic neuromuscular synapses (the Ca2 homolog, Dmca1A or cacophony, and the Ca1 homolog, Dmca1D) but with spatial and functional separation.

A quick and versatile protocol for the 3D visualization of transgene expression across the whole body of larval .

Larval are used as a genetically accessible study case in many areas of biological research. Here we report a fast, robust and user-friendly procedure for the whole-body multi-fluorescence imaging of larvae; the protocol has been optimized specifically for larvae by systematically tackling the pitfalls associated with clearing this small but cuticularized organism. Tests on various fluorescent proteins reveal that the recently introduced monomeric infrared fluorescent protein (mIFP) is particularly suitable for our approach.

Plasma membrane Ca ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca homeostasis in mice.

The amplitude and duration of Ca signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca signals in B cells have not been determined. In lymphocytes, plasma membrane Ca ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells.

Individual-level variability among trust criteria relevant to zoos and aquariums.

Prior research into the conceptual underpinnings of the public's institutional trust in zoos and aquariums has suggested a range of ethical dimensions that set these types of cultural institutions apart from others in the museum sector. As the recognized holders, care-takers, and nurturers of wild animals, zoos and aquariums are sustained at least in part by the public's perception that these activities are legitimate pursuits and essential to the long-term conservation of the natural world. This paper builds on recent research that identified the ethical dimensions of trust in zoos and aquariums and assessed their distribution among the U.

Integration of mechanical conditioning into a high throughput contractility assay for cardiac safety assessment.

Induction: Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. With the presented study, we aimed at validating the newly developed FLEXcyte96 technology with respect to physiological responses of hiPSC-CMs to pharmacological compounds with known inotropic and/or cardiotoxic effects.

Cell Survival Failure in Effector T Cells From Patients With Systemic Lupus Erythematosus Following Insufficient Up-Regulation of Cold-Shock Y-Box Binding Protein 1.

Objective: The importance of cold-shock Y-box binding protein 1 (YB-1) for cell homeostasis is well-documented based on prior observations of its association with certain cancer entities. This study was undertaken to explore the role of YB-1 in T cell homeostasis and survival and the potential contribution of YB-1 to the pathogenesis of systemic lupus erythematosus (SLE).

Methods: In the peripheral blood from 25 SLE patients and 25 healthy donors, the expression of YB-1 and frequency of T cell apoptosis was analyzed by quantitative polymerase chain reaction (qPCR) and fluorescence-activated cell sorting of CD4+ T cells ex vivo and also analyzed in T cells in vitro after 6 days of stimulation with anti-CD3-coupled or anti-CD3/anti-CD28-coupled microspheres.

Bassoon proteinopathy drives neurodegeneration in multiple sclerosis.

Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the neuronal somata of mice and patients with MS.

Click Chemistry (CuAAC) and Detection of Tagged Synthesized Proteins in .

Copper-catalyzed azide-alkyne-cycloaddition (CuAAC), also known as 'click chemistry' serves as a technique for bio-orthogonal, that is, bio-compatible labeling of macromolecules including proteins or lipids. Click chemistry has been widely used to covalently, selectively, and efficiently attach probes such as fluorophores or biotin to small bio-orthogonal chemical reporter groups introduced into macromolecules. In bio-orthogonal non-canonical amino acid tagging (BONCAT) and fluorescent non-canonical amino acid tagging (FUNCAT) proteins are metabolically labeled with a non-canonical, azide-bearing amino acid and subsequently CuAAC-clicked either to an alkyne-bearing biotin (BONCAT) for protein purification, Western blot, or mass spectrometry analyses or to an alkyne-bearing fluorophore (FUNCAT) for immunohistochemistry.

Implantable computer-controlled adaptive multielectrode positioning system.

Acute neuronal recordings performed with metal microelectrodes in nonhuman primates allow investigating the neural substrate of complex cognitive behaviors. Yet the daily reinsertion and positioning of the electrodes prevents recording from many neurons simultaneously, limiting the suitability of these types of recordings for brain-computer interface applications or for large-scale population statistical methods on a trial-by-trial basis. In contrast, chronically implanted multielectrode arrays offer the opportunity to record from many neurons simultaneously, but immovable electrodes prevent optimization of the signal during and after implantation and cause the tissue response to progressively impair the transduced signal quality, thereby limiting the number of different neurons that can be recorded over the lifetime of the implant.

A Wireless, Bidirectional Interface for In Vivo Recording and Stimulation of Neural Activity in Freely Behaving Rats.

In vivo electrophysiology is a powerful technique to investigate the relationship between brain activity and behavior at a millisecond and micrometer scale. However, current methods mostly rely on tethered cable recordings or only use unidirectional systems, allowing either recording or stimulation of neural activity, but not at the same time or same target. Here, a new wireless, bidirectional device for simultaneous multichannel recording and stimulation of neural activity in freely behaving rats is described.

A Presynaptic Function of Shank Protein in .

Human genetic studies support that loss-of-function mutations in the 3 domain and yrin repeat containing family proteins (SHANK1-3), the large synaptic scaffolding proteins enriched at the postsynaptic density of excitatory synapses, are causative for autism spectrum disorder and other neuropsychiatric disorders in humans. To better understand the functions of Shank and facilitate dissection of neuropathology associated with mutations in human, we generated multiple mutations in the gene, the only member of the SHANK family in Both male and female null mutants were fully viable and fertile with no apparent morphological or developmental defects. Expression analysis revealed apparent enrichment of Shank in the neuropils of the CNS.

A complex of Neuroplastin and Plasma Membrane Ca ATPase controls T cell activation.

The outcome of T cell activation is determined by mechanisms that balance Ca influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn ), an immunoglobulin superfamily protein, display elevated cytosolic Ca and impaired post-stimulation Ca clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca ATPases (PMCAs) as the main interaction partners of Neuroplastin.