Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.

TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance.

Engineering a probiotic Bacillus subtilis for acetaldehyde removal: A hag locus integration to robustly express acetaldehyde dehydrogenase.

We have addressed critical challenges in probiotic design to develop a commercially viable bacterial strain capable of removing the intestinal toxin, acetaldehyde. In this study, we report the engineering of the hag locus, a σD-dependent flagellin expression site, as a stable location for robust enzyme production. We demonstrate constitutive gene expression in relevant conditions driven by the endogenous hag promoter, following a deletion of the gene encoding a post-translational regulator of σD, FlgM, and a point mutation to abrogate the binding of the translational inhibitor CsrA.

Olfactory combinatorial coding supports risk-reward decision making in .

Olfactory-driven behaviors are essential for animal survival, but mechanisms for decoding olfactory inputs remain poorly understood. We have used whole-network Ca imaging to study olfactory coding in We show that the odorant 1-octanol is encoded combinatorially in the periphery as both an attractant and a repellant. These inputs are integrated centrally, and their relative strengths determine the sensitivity and valence of the behavioral response through modulation of locomotory reversals and speed.

The Impact of Using Standardized Autism Screening on Referral to Specialist Evaluation for Young Children on the Autism Spectrum: A Cluster-Randomized Controlled Trial.

Objective: We tested whether the implementation of standardized, high-fidelity screening for autism during routine well-child check-ups results in the following: increasing the number of children with suspected autism referred to diagnostic evaluation; lowering the age at which they are referred; and facilitating autism diagnosis for children across a more diverse range of demographic backgrounds and clinical presentations, including those with subtle manifestations.

Method: As part of a multi-site cluster randomized trial, pediatric practices were randomly assigned to an experimental condition involving training and supervision in the universal, standardized, high-fidelity implementation of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F), or a usual care condition. Children in both conditions identified as having a high likelihood of autism during well-child visits were referred to a diagnostic evaluation conducted by clinicians naive to referral source.