Biology subjects

Mohan, U.

Publications and source records attributed to Mohan, U..

3 recordsLinked to original sources

bioRxiv2023

Targeting staphylococcal cell-wall biosynthesis protein FemX through steered molecular dynamics and drug-repurposing approach

Staphylococcus aureus-mediated infection is a serious threat in this antimicrobial-resistant world. S. aureus has become a superbug by challenging conventional as well as modern treatment strategies. Nowadays, drug repurposing has become a new trend for the discovery of new drug molecules. This study focuses on evaluating FDA-approved drugs that can be repurposed against S. aureus infection. Steered molecular dynamics (SMD) has been performed for Lumacaftor and Olaparib against staphylococcal FemX to understand their binding to the active site. A time-dependent external force or rupture has been applied to the ligands to calculate the force required to dislocate the ligand from the binding pocket. SMD analysis indicates that Lumacaftor has a high affinity for the substrate binding pocket in comparison to Olaparib. Umbrella sampling exhibits that Lumacaftor possesses a higher free energy barrier to displace it from the ligand-binding site. The bactericidal activity of Lumacaftor and Olaparib has been tested, and it shows that Lumacaftor has shown moderate activity along with biofilm inhibition potential (MIC value with conc. 128 g/mL). Pharmacokinetic and toxicology evaluations indicate that Lumacaftor has higher pharmacokinetic potential with lower toxicity. This is the first experimental report where staphylococcal FemX has been targeted for the discovery of new drugs. It is suggested that Lumacaftor may be a potential lead molecule against S. aureus.

pharmacology and toxicology↗

bioRxiv2022

Small-amplitude head oscillations result from a multimodal head stabilization reflex in hawkmoths

In flying insects, head stabilization is an important reflex which helps to reduce motion blur during fast aerial maneuvers. This reflex is multimodal and requires the integration of visual and antennal mechanosensory feedback, each operating as a negative-feedback control loop. As in any negative-feedback system, the head stabilization system possesses inherent oscillatory dynamics that depends on the rates and latencies of the sensorimotor components constituting the reflex. Consistent with this expectation, we observed small amplitude oscillations in the head motion (or head wobble) of the Oleander hawkmoth Daphnis nerii. We show here that these oscillations emerge from the inherent dynamics of the multimodal reflex that underlies gaze stabilization, and the amplitude of the head wobble is a function of both the visual feedback and antennal mechanosensory feedback from the Johnstons organs. The head wobble is thus an outcome of a multimodal, dynamically-stabilized head positioning reflex.

neuroscience↗

bioRxiv2022

Integration of visual and antennal mechanosensory feedback during head stabilization in hawkmoths

During flight maneuvers, insects exhibit compensatory head movements which are essential for stabilizing the visual field on their retina, reducing motion blur, and supporting visual self-motion estimation. In Diptera, such head movements are mediated via visual feedback from their compound eyes that detect retinal slip, as well as rapid mechanosensory feedback from their halteres - the modified hindwings that sense the angular rates of body rotations. Because non-Dipteran insects lack halteres, it is not known if mechanosensory feedback about body rotations plays any role in their head stabilization response. Diverse non-Dipteran insects are known to rely on visual and antennal mechanosensory feedback for flight control. In hawkmoths, for instance, reduction of antennal mechanosensory feedback severely compromises their ability to control flight. Similarly, when the head movements of freely-flying moths are restricted, their flight ability is also severely impaired. The role of compensatory head movements as well as multimodal feedback in insect flight raises an interesting question: in insects that lack halteres, what sensory cues are required for head stabilization? Here, we show that in the nocturnal hawkmoth Daphnis nerii, compensatory head movements are mediated by combined visual and antennal mechanosensory feedback. We subjected tethered moths to open-loop body roll rotations under different lighting conditions, and measured their ability to maintain head angle in the presence or absence of antennal mechanosensory feedback. Our study suggests that head stabilization in moths is mediated primarily by visual feedback during roll movements at lower frequencies, whereas antennal mechanosensory feedback is required when roll occurs at higher frequency. These findings are consistent with the hypothesis that control of head angle results from a multimodal feedback loop that integrates both visual and antennal mechanosensory feedback, albeit at different latencies. At adequate light levels, visual feedback is sufficient for head stabilization. However, under dark conditions, antennal mechanosensory feedback is essential for the control of head movements. HighlightsO_LIVisual feedback contributes to head stabilization primarily during slower body rotation in hawkmoths. C_LIO_LIAntennal mechanosensors contribute to head stabilization primarily during faster body roll. C_LIO_LIAntennal mechanosensory feedback in head stabilization is mediated via Johnstons organ. C_LIO_LIRestricting head movements affects flight control. C_LI

animal behavior and cognition↗