The β-Secretase Substrate Seizure 6–Like Protein (SEZ6L) Controls Motor Functions in Mice

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases.

An Artificial Optoelectronic Nociceptor Based on In2S3 Memristor

Nociceptors are an indispensable part of the human nervous system that can sense potential dangers from external environmental stimuli. The biomimetic studies of artificial nociceptors have inspired advanced technology in neuromorphic computing, humanoid robots and artificial visual sensors. In this work, we demonstrate an artificial optoelectronic nociceptor using the memristor of large-area In2S3 thin films. The nociceptor responses not only to electrical stimuli but also illumination of visual light, showing complete nociceptive behaviors of "threshold", "inadaptation", "flabby" and "sensitization". The features of the sensory signal such as responding threshold, relaxation time and sensitivity can be tuned in controllable manner, by the strength and frequency of the external stimuli as well as the biasing of electrostatic gate. Such realization of sensory response to multiple external stimuli in the artificial perceptron demonstrates the feasibility of constructing advanced electronic receptor and artificial human eye.

A Histopathology Model of Astrocytoma

Neoplastic transformation occurs in all glial cell types of the human nervous system, producing a wide variety of clinic-pathological entities and morphological variants. As the molecular events responsible for astrocytoma formation and progression are being clarified, it is becoming possible to correlate these alterations with the specific histopathological and biological features of astrocytoma, anaplastic astrocytoma and glioblastoma multiforme. Diagnosis, treatment, and prognostication in brain stem astrocytoma’s have been hindered by the occurrence in the same site of two distinct pathological entities-fibrillary and pilocytic astrocytoma. The small size of the specimens from this region adds an additional confounding factor in tumor classification. Nevertheless, histological assignment to either of these two prognostically different categories is often possible, especially if the importance of this distinction is recognized. In the face of a nonspecific histological diagnosis, e.g. "low-grade astrocytoma', certain radiographic and clinical features may, in combination with the pathological findings, be useful in tumor subclassification.

Comparison of Different Tissue Clearing Methods for Three-Dimensional Reconstruction of Human Brain Cellular Anatomy Using Advanced Imaging Techniques

The combination of tissue clearing techniques with advanced optical microscopy facilitates the achievement of three-dimensional (3D) reconstruction of macroscopic specimens at high resolution. Whole mouse organs or even bodies have been analyzed, while the reconstruction of the human nervous system remains a challenge. Although several tissue protocols have been proposed, the high autofluorescence and variable post-mortem conditions of human specimens negatively affect the quality of the images in terms of achievable transparency and staining contrast. Moreover, homogeneous staining of high-density epitopes, such as neuronal nuclear antigen (NeuN), creates an additional challenge. Here, we evaluated different tissue transformation approaches to find the best solution to uniformly clear and label all neurons in the human cerebral cortex using anti-NeuN antibodies in combination with confocal and light-sheet fluorescence microscopy (LSFM). Finally, we performed mesoscopic high-resolution 3D reconstruction of the successfully clarified and stained samples with LSFM.

‘The Opium-Eater Boasteth Himself to be a Philosopher’: Bodily Subjection and Intellectual Self-fashioning in De Quincey's 1821 ‘Confessions’

De Quincey's assertion in the 1821 ‘Confessions’ that the effects of opium were ‘always, and in the highest degree, to excite and stimulate the system’, establishes him in contemporary medical discourse as a follower of Brunonianism. Yet, against this indubitably pharmacological and bodily strain, the ‘Confessions’ also insists upon an intellectual aspect to the opium-eater's dreaming, his ability to dream imaginatively. This essay seeks to relate these discursive tensions in De Quincey, rooted in Enlightenment ideas of the human nervous system held in equilibrium, to his self-presentation as an addict and a philosopher in his autobiographical writings, and to his critical thinking. As I argue, the physiological theory of Brunonianism in the ‘Confessions’ is complemented by an equal emphasis on moral and intellectual development embedded in the ideas of Hartleian psychology which provide a balancing view of body and (embodied) mind in De Quincey's thinking.

Basic locomotor muscle synergies used in land walking are finely tuned during underwater walking

Underwater walking is one of the most common hydrotherapeutic exercises. Therefore, understanding muscular control during underwater walking is important for optimizing training regimens. The effects of the water environment on walking are mainly related to the hydrostatic and hydrodynamic theories of buoyancy and drag force. To date, muscular control during underwater walking has been investigated at the individual muscle level. However, it is recognized that the human nervous system modularly controls multiple muscles through muscle synergies, which are sets of muscles that work together. We found that the same set of muscle synergies was shared between the two walking tasks. However, some task-dependent modulation was found in the activation combination across muscles and temporal activation patterns of the muscle synergies. The results suggest that the human nervous system modulates activation of lower-limb muscles during water walking by finely tuning basic locomotor muscle synergies that are used during land walking to meet the biomechanical requirements for walking in the water environment.

Overview of the modeling of complex biological systems and its role in neurosurgery

Biological systems are complex with distinct characteristics such as nonlinearity, adaptability, and self-organization. Biomedical research has helped in advancing our understanding of certain components the human biology but failed to illustrate the behavior of the biological systems within. This failure can be attributed to the use of the linear approach, which reduces the system to its components then study each component in isolation. This approach assumes that the behavior of complex systems is the result of the sum of the function of its components. The complex systems approach requires the identification of the components of the system and their interactions with each other and with the environment. Within neurosurgery, this approach has the potential to advance our understanding of the human nervous system and its subsystems.