bioRxiv Science⌕ Search

Biology subjects

Olson, G.

Publications and source records attributed to Olson, G..

3 recordsLinked to original sources

Loss of calcium-binding protein Cbp53E leads to delayed repolarization of photoreceptor cells in Drosophila

Calcium functions as an important second messenger in a wide variety of intracellular processes. In photoreceptor cells, calcium is involved in activation, deactivation, and adaptation in response to light stimuli. Calcium-binding protein 53E (Cbp53E, also known as calbindin-32 or cbn), a protein with 6 EF-Hand domains thought to act as a calcium buffer, was previously identified to have elevated expression levels in the eye of drosophila. While a recent study showed that transgenic flies lacking Cbp53E have aberrant axonal arborization at the neuromuscular junction, nothing is known about the role of Cbp53E in the visual system. We performed electroretinogram (ERG) recordings on Cbp53E mutant flies to test whether eye function was affected. Here, we report that Cbp53E null mutants exhibit a prolonged repolarization (or slow termination) phenotype which can be rescued by expressing Cbp53E in photoreceptor cells. The human homologs Calbindin 2, Calbindin 1, and S100G also rescue the Drosophila ERG phenotype. This supports a role for Cbp53E in regulating intracellular calcium levels of photoreceptor cells and contributing to normal sensory neuron response dynamics in vivo in Drosophila and suggests a similar function in human photoreceptor cells as well.

neuroscience↗

Adjustable Compliance Footwear Technology to Investigate Gait Adaptation

Kinetic asymmetries in gait caused by neurological impairments are a major factor in mobility deficiency. Gait perturbation training has shown promise for rehabilitating neurological gait asymmetry, but the transfer of benefits from treadmill training to overground walking is limited. To enable kinetic gait perturbation training on treadmills and overground, we developed novel adjustable compliance footwear technology. The system consists of a wearable pneumatic actuation module which controls the pressure of custom air pockets embedded in a soft lattice midsole, and is capable of independently and wirelessly adjusting the midsole compliance under each foot from 300 kN/m and 60% energy absorption to 18 kN/m and 75% energy absorption in under 4 seconds. Hindfoot and forefoot sole deflection data are measured via Hall effect sensors and paired magnets characterized to 1.7 mm accuracy. To demonstrate the experimental capability of the system, we successfully triggered multiple compliance changes during overground walking and recorded ground reaction forces and embedded sensor values during a prolonged asymmetric compliance walking bout on a treadmill. Future work will include a full experimental study of gait adaptation to asymmetric footwear compliance perturbations.

bioengineering↗

Computational approaches identify novel transcription factor combinations that promote corticospinal axon growth following injury

Transcription factors (TFs) act as powerful levers to regulate neural physiology and can be targeted to improve cellular responses to injury or disease. Because TFs often depend on cooperative activity, a major challenge is to identify and deploy optimal sets. Here we developed a novel bioinformatics pipeline, centered on TF co-occupancy of regulatory DNA, and used it to predict factors that potentiate the effects of pro-regenerative Klf6. High content screens of neurite outgrowth identified cooperative activity by 12 candidates, and systematic testing in an animal model of corticospinal tract (CST) damage substantiated three novel instances of pairwise cooperation. Combined Klf6 and Nr5a2 drove the strongest growth, and transcriptional profiling of CST neurons identified Klf6/Nr5a2-responsive gene networks involved in macromolecule biosynthesis and DNA repair. These data identify novel TF combinations that promote enhanced CST growth, clarify the transcriptional correlates, and provide a bioinformatics roadmap to detect TF synergy.

neuroscience↗