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    Analyzing Gaze and Hand Movement Patterns in Leader-Follower Interactions During a Time-Continuous Cooperative Manipulation Task

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    In daily life, people often interact by taking on leader and follower roles. Unlike laboratory experiments, these interactions unfold naturally and continuously. Although it is well established that gaze typically precedes object manipulation, much less is known about how gaze–hand patterns evolve in interactive settings where one person must take the other’s actions into account. Here we examine predictive, planning-related behavior in a two-player tabletop game called “do-undo.” Participants alternated as Leader and Follower. The Leader performed simple pick-and-place actions to alter the arrangement of objects, while the Follower used other objects to restore the previous configuration. We recorded eye and hand movements, along with object trajectories, using a system that combined eye tracking with multi-camera motion capture. Touch sensors on the players’ hands provided precise timing of contacts, allowing us to segment cooperative action into well-defined temporal intervals. As expected, eye fixations consistently preceded manipulation, but clear role differences emerged. Leaders looked more often and earlier at target objects. In many trials, their gaze anticipated not only their own actions but also those required of the Follower. Leaders also more frequently checked the outcome of the do-undo sequence. Both roles showed gaze patterns consistent with memorization, but alternating gazes between objects and destinations were much more common in Leaders. Some patterns suggested longer-term planning beyond the immediate action. These findings reveal distinct decision-making and planning strategies in Leaders and Followers. Leaders consider not only their own next moves but also the potential actions of their partners, shedding light on the complex cognitive processes that underly everyday human interaction

    Phosphorylation of presynaptic PLPPR3 controls synaptic vesicle release

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    Phospholipid-phosphatase-related protein 3 (PLPPR3) belongs to a family of transmembrane proteins highly expressed in the nervous system where it regulates critical axonal growth processes during guidance, filopodia formation, and branching. However, little is known regarding its role in synapses and the signaling events regulating PLPPR3 function. Here, we identify 26 high-confidence phosphorylation sites in the intracellular domain of PLPPR3 using mass spectrometry. Biochemical characterization established one of these-S351-as a bona fide phosphorylation site of protein kinase A (PKA). PLPPR3 is enriched at presynaptic terminals, and deletion of PLPPR3 results in increased depolarization-induced synaptic vesicle release in hippocampal neurons. This tonic inhibitory signal toward depolarization-induced presynaptic activity is corrected by expression of PLPPR3 intracellular domain, but not a S351A phospho-dead mutant, in Plppr3 -/- hippocampal neurons. We propose that PLPPR3 phosphorylation under the control of PKA activity is a signaling integrator of presynaptic activity in hippocampal neurons

    SV2A-PET imaging uncovers cortical synapse loss in multiple sclerosis

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    Gray matter pathology, including the formation of cortical lesions, predicts progression in people with multiple sclerosis (PwMS). Here, we investigated whether positron emission tomography (PET) imaging using the synaptic vesicle protein 2A (SV2A)-targeting radioligand [18F]UCB-H could help to detect and monitor synapse loss, an early feature of gray matter pathology in MS. First, we confirmed that SV2A is a suitable marker of synapse density in MS by analyzing SV2A mRNA and protein expression in cortical gray matter. We then used a mouse model of cortical MS pathology to demonstrate that SV2A-PET imaging can detect synapse loss in cortical lesions and that synapse densities measured by PET imaging correspond to the densities of genetically and immunohistochemically labeled synapses in the same lesions. Last, we performed SV2A-PET imaging in a total of 31 PwMS at different stages of the disease process, showing that PET imaging can detect synapse loss in cortical MS lesions in vivo. Moreover, we found that interhemispheric asymmetries in SV2A-PET tracer uptake can be leveraged to uncover further cortical alterations, the volume of which was more than 20-fold larger than the cortical lesion area detected by MRI. The extent of these PET-defined areas of cortical synapse pathology was larger in the progressive stage of the disease and correlated with the disability and cognitive performance of the same individuals. SV2A-PET imaging thus unmasked clinically relevant cortical pathology in MS thereby providing a promising tool to detect and monitor disease progression

    Neopterin as a Tool for Primate Ecoimmunology: Current Knowledge, Practical Application, and New Directions From Captivity to the Wild

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    Neopterin is a well-established biomarker of interferon-gamma-mediated macrophage activation that indicates cell-mediated immune system responses in humans. Because it is readily quantifiable in urine, it is increasingly used in nonhuman primates to study cell-mediated immune functioning in relation to infectious diseases, but also environmental and individual factors, in both captive and wild primates. This review synthesizes our current knowledge on these topics with a focus on nonhuman primates. We cover the influence of various methodological factors during sampling and analysis on the reliability of neopterin measurements and give practical advice on how these factors can be mitigated. Furthermore, we address the advantages and disadvantages of different biological matrices in which neopterin can be measured and propose best practice guidelines for handling and storage of samples that consider challenges encountered during fieldwork. We conclude this review with an outlook on topics within primatology where neopterin, as a marker of cell-mediated immune functioning, could become a valuable tool to answer applied questions and test evolutionary hypotheses about immune functioning in primates

    Behavioral relevance of category selectivity revealed by human ECoG data

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    Object recognition is a crucial brain function that involves a complex interplay between various brain regions. However, the behavioral relevance of functional interactions between these regions remains largely unexplored. In this study, we examined the functional interactions between different brain regions during object recognition using intracranial electrocorticography (ECoG) recordings in subjects diagnosed with pharmacologically intractable epilepsy. We computed the phase locking value (PLV) between different brain areas and its category selectivity, and assessed its behavioral relevance by comparing correctly and incorrectly performed trials. Our results revealed that phase locking between brain regions varies across different object categories and that this variability significantly influences the perceptual behavior of subjects. Importantly, we found that the behavioral relevance of these interactions is spatially organized, with the high behaviorally relevant connections being longer for the frontal lobe and shorter for the occipital lobe. These findings underscore the unique roles of different brain areas in object recognition and pave the way for more nuanced explorations of the interplay between brain regions in object recognition and other cognitive functions

    Metabolic Changes in Living Human Lymphoma Cells Intervening NAD + Metabolism as Revealed by NAD (P)H‐Fluorescence Lifetime Imaging and Para‐Hydrogen‐Induced Polarization NMR

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    ABSTRACT Proliferating cells have a sustained high demand for regeneration of electron acceptors as nicotinamide dinucleotide (phosphate) (NAD(P) + /NAD(P)H) is involved in a number of critical redox reactions within cells. However, their analysis in living cells is still challenging. We propose that combining label‐free NADH and NADPH fluorescence lifetime imaging (NAD(P)H‐FLIM) and signal‐enhanced nuclear magnetic resonance (NMR) spectroscopy allows new, deeper insights into changes in specific metabolic pathways in living cells. For proof of principle, NAD + ‐metabolism was perturbed by specific inhibition of the rate‐limiting enzyme of the NAD + “Salvage pathway” Nicotinamide phosphoribosyltransferase (NAMPT) by FK866 in RAMOS human lymphoma cells. FK866 treatment leads to NAD(H) reduction, followed by reduced RAMOS cell proliferation. The NAD(P)H‐FLIM analysis revealed increased general NAD(P)H‐dependent metabolic activity indicated by increased ratios of enzyme‐bound to total NAD(P)H concentration upon NAMPT inhibition. More importantly, a marked reduction in lactate dehydrogenase (LDH) activity accompanied by NADPH oxidase activity increase is observed. Using signal‐enhanced NMR spectroscopy a reduced flux of pyruvate to lactate catalyzed by LDH is detectable in real time in living cells. This strongly supports NAD(P)H‐FLIM analysis and demonstrates that intervening in the NAD + “Salvage pathway” can have specific and global consequences for cells. Our principle study shows how spatially‐resolved metabolic imaging techniques, that is, NAD(P)H‐FLIM, are complemented by real‐time NMR, paving the way toward a comprehensive spatiotemporal understanding of metabolic pathways in living cells.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659HORIZON EUROPE European Research Council https://doi.org/10.13039/10001918

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