Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis

Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age-and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200-1,400 bacterial genomes/cm(3) and low bacterial rRNA: rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients' WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients' WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms

Swept-frequency feedback interferometry using terahertz frequency QCLs: a method for imaging and materials analysis

The terahertz (THz) frequency quantum cascade laser (QCL) is a compact source of high-power radiation with a narrow intrinsic linewidth. As such, THz QCLs are extremely promising sources for applications including high-resolution spectroscopy, heterodyne detection, and coherent imaging. We exploit the remarkable phase-stability of THz QCLs to create a coherent swept-frequency delayed self-homodyning method for both imaging and materials analysis, using laser feedback interferometry. Using our scheme we obtain amplitude-like and phase-like images with minimal signal processing. We determine the physical relationship between the operating parameters of the laser under feedback and the complex refractive index of the target and demonstrate that this coherent detection method enables extraction of complex refractive indices with high accuracy. This establishes an ultimately compact and easy-to-implement THz imaging and materials analysis system, in which the local oscillator, mixer, and detector are all combined into a single laser