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Objective: Leukodystrophies are a diverse group of rare inherited disorders that affect the white matter of the central nervous system with a wide phenotypic spectrum. We aimed to characterize the clinical and genetic features of leukodystrophies in a central‐southern Chinese cohort. Methods: A cohort of 16 Chinese probands with leukodystrophy was recruited and performed genetic analysis by targeted panels or whole‐exome sequencing. Further functional analysis of identified mutations in the colony stimulating factor 1 receptor (CSF1R) gene was explored. Results: A total of eight pathogenic variants (3 novel, 5 documented) were identified in genes including AARS2, ABCD1, CSF1R, and GALC. Common symptoms of leukodystrophy such as cognitive decline, behavioral symptoms, bradykinesia, and spasticity were observed in mutation carriers as well as other rare features (e.g., seizure, dysarthric, and vision impairment). Overexpressing CSF1R mutants p.M875I and p.F971Sfs*7 in vitro showed pronounced cleavage CSF1R and suppressed protein expression, respectively, and reduced transcripts of both mutants were observed. CSF1 treatment revealed deficient and suppressed CSF1R phospho‐activation with the mutants. In contrast to the plasma membrane and endoplasmic reticulum (ER) localized wild‐type CSF1R, M875I mutant showed much less membrane association and greater detainment in the ER, whereas F971Sfs*7 mutation led to aberrant non‐ER localization. Both mutations caused suppressed cell viability, which was partially resulted from deficient/suppressed CSF1R‐ERK signaling. Interpretation: In summary, our findings expand the mutation spectrum of these genes in leukodystrophies. Supported by in vitro validation of the pathogenicity of heterozygous CSF1R mutations, our data also provide insights into the pathogenic mechanisms of CSF1R‐related leukodystrophy. [ABSTRACT FROM AUTHOR]

Surgical resection of lesions and closed‐loop suppression are the two main treatment options for patients with refractory epilepsy whose symptoms cannot be managed with medicines. Unfortunately, failures in foci localization and seizure prediction are constraining these treatments. Electrical impedance tomography (EIT), sensitive to impedance changes caused by blood flow or cell swelling, is a potential new way to locate epileptic foci and predict seizures. Animal validation is a necessary research process before EIT can be used in clinical practice, but it is unclear which among the many animal epilepsy models is most suited to this task. The selection of an animal model of epilepsy that is similar to human seizures and can be adapted to EIT is important for the accuracy and reliability of EIT research results. This study provides an overview of the animal models of epilepsy that have been used in research on the use of EIT to locate the foci or predict seizures; discusses the advantages and disadvantages of these models regarding inducement by chemical convulsant and electrical stimulation; and finally proposes optimal animal models of epilepsy to obtain more convincing research results for foci localization and seizure prediction by EIT. The ultimate goal of this study is to facilitate the development of new treatments for patients with refractory epilepsy. This article is categorized under:Neuroscience > Clinical NeurosciencePsychology > Brain Function and Dysfunction [ABSTRACT FROM AUTHOR]

Efficient optical coupling between nano‐ and macroscale areas is strongly suppressed by the diffraction limit. This work presents a possible solution to this fundamental problem via the experimental fabrication, characterization, and comprehensive theoretical analysis of structures referred to as "photonic funnels." The funnels represent a novel composite material platform that combines hyperbolic dielectric response with geometry‐assisted optical confinement. Experimentally, funneling of mid‐infrared light through openings with diameters as small as 1/25th of the free space wavelength (λ0) is demonstrated. By analyzing the optical response of the funnels, as fabricated, both confinement of mid‐infrared radiation to the λ0/25 areas and efficient outcoupling of light from deep subwavelength areas are confirmed. [ABSTRACT FROM AUTHOR]