Molecular subtypes of ALS are associated with differences in patient prognosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease with poorly understood clinical heterogeneity, underscored by significant differences in patient age at onset, symptom progression, therapeutic response, disease duration, and comorbidity presentation. We perform a patient stratification analysis to better understand the variability in ALS pathology, utilizing postmortem frontal and motor cortex transcriptomes derived from 208 patients. Building on the emerging role of transposable element (TE) expression in ALS, we consider locus-specific TEs as distinct molecular features during stratification. Here, we identify three unique molecular subtypes in this ALS cohort, with significant differences in patient survival. These results suggest independent disease mechanisms drive some of the clinical heterogeneity in ALS.

Automated microscope-independent fluorescence-guided micropipette.

Glass micropipette electrodes are commonly used to provide high resolution recordings of neurons. Although it is the gold standard for single cell recordings, it is highly dependent on the skill of the electrophysiologist. Here, we demonstrate a method of guiding micropipette electrodes to neurons by collecting fluorescence at the aperture, using an intra-electrode tapered optical fiber. The use of a tapered fiber for excitation and collection of fluorescence at the micropipette tip couples the feedback mechanism directly to the distance between the target and electrode. In this study, intra-electrode tapered optical fibers provide a targeted robotic approach to labeled neurons that is independent of microscopy.

Side-viewing photoacoustic waveguide endoscopy.

Side-viewing hollow optical waveguides allow for minimally invasive endoscopy by concentrically guiding light and sound for photoacoustic generation and detection. Here, we characterize the side-viewing photoacoustic waveguide (PWG) endoscope by scanning 7.2 µm diameter carbon fiber threads within phantom tissues and animal tissues. Photoacoustic signals are carried along the 5.5 and 10.0 cm length of the PWG with minimal attenuation. Thus, this technology enables 360°, deep-tissue photoacoustic imaging. Photoacoustic signals were identified up to 8.0 mm from the PWG imaging window in an optically clear medium. The outer diameter of this device is measured as just over 1.0 mm, with the potential to be further miniaturized due to its unique design. The PWG is an ideal candidate for a myriad of pre-clinical and clinical applications where typical photoacoustic endoscopy systems are impractical, due to their size. Presented here, is the first side-viewing photoacoustic waveguide endoscope.