254 research outputs found
Mannose 6-phosphate-specific receptor is a transmembrane protein with a C-terminal extension oriented towards the cytosol
Virtual Electrode Recording Tool for EXtracellular potentials (VERTEX): Comparing multi-electrode recordings from simulated and biological mammalian cortical tissue
Local field potentials (LFPs) sampled with extracellular electrodes are
frequently used as a measure of population neuronal activity. However, relating
such measurements to underlying neuronal behaviour and connectivity is
non-trivial. To help study this link, we developed the Virtual Electrode
Recording Tool for EXtracellular potentials (VERTEX). We first identified a
reduced neuron model that retained the spatial and frequency filtering
characteristics of extracellular potentials from neocortical neurons. We then
developed VERTEX as an easy-to-use Matlab tool for simulating LFPs from large
populations (>100 000 neurons). A VERTEX-based simulation successfully
reproduced features of the LFPs from an in vitro multi-electrode array
recording of macaque neocortical tissue. Our model, with virtual electrodes
placed anywhere in 3D, allows direct comparisons with the in vitro recording
setup. We envisage that VERTEX will stimulate experimentalists, clinicians, and
computational neuroscientists to use models to understand the mechanisms
underlying measured brain dynamics in health and disease.Comment: appears in Brain Struct Funct 201
Researching interactions between humans and machines: methodological challenges
Communication scholars are increasingly concerned with interactions between humans and communicative agents. These agents, however, are considerably different from digital or social media: They are designed and perceived as life-like communication partners (i.e., as “communicative subjects”), which in turn poses distinct challenges for their empirical study. Hence, in this paper, we document, discuss, and evaluate potentials and pitfalls that typically arise for communication scholars when investigating simulated or non-simulated interactions between humans and chatbots, voice assistants, or social robots. In this paper, we focus on experiments (including pre-recorded stimuli, vignettes and the “Wizard of Oz”-technique) and field studies. Overall, this paper aims to provide guidance and support for communication scholars who want to empirically study human-machine communication. To this end, we not only compile potential challenges, but also recommend specific strategies and approaches. In addition, our reflections on current methodological challenges serve as a starting point for discussions in communication science on how meaning-making between humans and machines can be investigated in the best way possible, as illustrated in the concluding section
Four monoclonal antibodies inhibit the recognition of arylsulphatase A by the lysosomal enzyme phosphotransferase
Restoration of arylsulphatase A activity in human-metachromatic-leucodystrophy fibroblasts via retroviral-vector-mediated gene transfer
Parkinson's disease-linked mutations in VPS35 induce dopaminergic neurodegeneration
Mutations in the vacuolar protein sorting 35 homolog (VPS35) gene at the PARK17 locus, encoding a key component of the retromer complex, were recently identified as a new cause of late-onset, autosomal dominant Parkinson's disease (PD). Here we explore the pathogenic consequences of PD-associated mutations in VPS35 using a number of model systems. VPS35 exhibits a broad neuronal distribution throughout the rodent brain, including within the nigrostriatal dopaminergic pathway. In the human brain, VPS35 protein levels and distribution are similar in tissues from control and PD subjects, and VPS35 is not associated with Lewy body pathology. The common D620N missense mutation in VPS35 does not compromise its protein stability or localization to endosomal and lysosomal vesicles, or the vesicular sorting of the retromer cargo, sortilin, SorLA and cation-independent mannose 6-phosphate receptor, in rodent primary neurons or patient-derived human fibroblasts. In yeast we show that PD-linked VPS35 mutations are functional and can normally complement VPS35 null phenotypes suggesting that they do not result in a loss-of-function. In rat primary cortical cultures the overexpression of human VPS35 induces neuronal cell death and increases neuronal vulnerability to PD-relevant cellular stress. In a novel viral-mediated gene transfer rat model, the expression of D620N VPS35 induces the marked degeneration of substantia nigra dopaminergic neurons and axonal pathology, a cardinal pathological hallmark of PD. Collectively, these studies establish that dominant VPS35 mutations lead to neurodegeneration in PD consistent with a gain-of-function mechanism, and support a key role for VPS35 in the development of PD
Different Origins of Gamma Rhythm and High-Gamma Activity in Macaque Visual Cortex
High-gamma (80–200 Hz) activity can be dissociated from gamma rhythms in
the monkey cortex, and appears largely to reflect spiking activity in the
vicinity of the electrode
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