Kulkarni, Y. | bioRxiv Science

bioRxiv2025

Collective Response of ON and OFF Bipolar Cells to Light Contributes to Improved Visual Acuity

In the visual signal relay, retinal bipolar cells transduce neurotransmitter signals from photoreceptor cells into electrical signals for onward transmission to the brain. The electrical activity of bipolar cells is reflected in the b-wave of the electroretinogram which is majorly contributed by ON bipolar cells leading to the currently accepted belief that light-induced signals travel through these cells only. Here, we probe the role of ON and OFF pathways to generate visual percept under the hypothesis that the ON Bipolar Cell fine image (central illumination) is superimposed onto a coarser image formed due to OFF Bipolar Cell (surround illumination). This improves image sharpness through edge detection by unsharp masking, thereby contributing to improved visual acuity. This new finding could be useful in stimulating the retina through sub-retinal implants to restore vision.

neuroscience↗

bioRxiv2023

A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides.

The cellular imbalance between high concentrations of ribonucleotides (NTPs) and low concentrations of deoxyribonucleotides (dNTPs), is challenging for DNA polymerases when building DNA from dNTPs. It is currently believed that DNA polymerases discriminate against NTPs through a steric gate model involving a clash between a tyrosine and the 2-hydroxyl of the ribonucleotide in the polymerase active site in B-family DNA polymerases. With the help of crystal structures of a B-family polymerase with a UTP or CTP in the active site, molecular dynamics simulations, biochemical assays and yeast genetics, we have identified a mechanism by which the finger domain of the polymerase sense NTPs in the polymerase active site. In contrast to the previously proposed polar filter, our experiments suggest that the amino acid residue in the finger domain senses ribonucleotides by steric hindrance. Furthermore, our results demonstrate that the steric gate in the palm domain and the sensor in the finger domain are both important when discriminating NTPs. Structural comparisons reveal that the sensor residue is conserved among B-family polymerases and we hypothesize that a sensor in the finger domain should be considered in all types of DNA polymerases.

biochemistry↗