Biocon (United States)

SUMMARYKinesins are canonical molecular motors but can also function as modulators of intracellular signaling. KIF26A, an unconventional kinesin that lacks motor activity, inhibits growth factor receptor bound protein 2 (GRB2)- and focal adhesion kinase (FAK)-dependent signal transduction, but its functions in the brain have not been characterized. We report a patient cohort with biallelic loss-of-function variants in KIF26A, exhibiting a spectrum of congenital brain malformations. In the developing brain, KIF26A is preferentially expressed during early and mid-gestation in excitatory neurons. Combining mice and human iPSC-derived organoid models, we discovered that loss of KIF26A causes excitatory neuron-specific defects in radial migration, localization, dendritic and axonal growth, and apoptosis, offering a convincing explanation of the disease etiology in patients. Single-cell RNA-sequencing in KIF26A knock-out organoids revealed transcriptional changes in MAPK, MYC and E2F pathways. Our findings illustrate the pathogenesis of KIF26A loss-of-function variants, and identify the surprising versatility of this non-motor kinesin.

The three-dimensional ultrasonic anemometer (3DUA) is an instrument that can measure airflow velocities in three axes simultaneously. From the data gathered, airflow direction and air tubulence intensity may be determined. Using a propietary software package, results are available immediately on-line, in either a tabular or graphic format. This instrument was initially chosen to evaluate the performance of a new cleanroom ceiling system that had integrated the lighting and sprinklers within the filter support grid. Additional work was later performed to evaluate the impact of a membrane ceiling on a turbulent air supply.