Biology subjects

Patil, S. B.

Publications and source records attributed to Patil, S. B..

3 recordsLinked to original sources

bioRxiv2022

Multibody kinematic optimisation vs body fat: A performance analysis

We have analysed the performance of mulitbody kinematic optimisation methods in reducing soft tissue artefacts for subject data of varying body fat percentages. Multibody kinematic optimisation methods are a critical aspect of movement analysis using musculoskeletal modelling software. By minimising soft tissue artefacts, they help in achieving higher fidelity joint kinematics and dynamics analyses. Prior studies have not examined the performance of multibody kinematic optimisation on subjects of varying body fat percentages. Herein, we: 1) have analysed the efficacy of three different multibody kinematic optimisation methods on varying body fat percentages, 2) implemented a novel weighting scheme to reduce error irrespective of body fat percentages. Residual error using gait data of 50 participants of varying body fat percentages was calculated through inverse kinematic analysis using OpenSim(c) musculoskeletal modelling software. The analysis was repeated using a time-based weighting scheme. The residual error of participants with higher body fat percentages was greater by 30% when compared to residual error of participants of lower body fat percentages. Additionally, time-based weighting scheme reduced residual error by 20% on average compared to constant-value weighting scheme. Our results indicate that multibody kinematic optimisation methods are adversely affected by higher body fat percentages and that time-based weighting can provide higher fidelity movement analysis irrespective of body fat percentages. Through our results we aim to develop tools which provide greater precision in obesity-related movement analysis. Such tools could also help address the disparities in rates of obesity associated with different ethnic or socioeconomic background.

bioengineering↗

bioRxiv2020

Sucrose represses the expression of the strigolactone signalling gene D3/RMS4/MAX2 to promote tillering

- Shoot branching, a major component of shoot architecture, is regulated by multiple signals. Previous studies have indicated that sucrose may promote branching through suppressing the inhibitory effect of the hormone strigolactone (SL). However, the molecular mechanisms underlying this effect are unknown. - Here we used molecular and genetic tools to identify the molecular targets underlying the antagonistic interaction between sucrose and SL. - We showed that sucrose antagonises the suppressive action of SL on tillering in rice and on the degradation of D53, a major target of SL signalling. Sucrose inhibits the expression of D3, the orthologue of the arabidopsis F-box protein MAX2 required for SL signalling. Over-expression of D3 prevents sucrose from inhibiting D53 degradation and enabled the SL inhibition of tillering under high sucrose. Sucrose also prevents SL-induced degradation of D14, the SL receptor involved in D53 degradation. Interestingly, D14 over-expression enhances D53 protein levels and sucrose-induced tillering. - Our results show that sucrose inhibits SL perception by targeting key components of SL signalling and, together with previous studies reporting the inhibition of SL synthesis by nitrate and phosphate, demonstrate the central role played by strigolactones in the regulation of plant architecture by nutrients.

plant biology↗

bioRxiv2020

Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle

The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword. Serotype 1 ST306, a widespread pneumococcal clone, harbours a non-hemolytic variant of pneumolysin (Ply-NH). Performing crystal structure analysis of Ply-NH, we identified Y150H and T172I as key substitutions responsible for loss of its pore forming activity. We uncovered a novel inter-molecular cation-{pi} interaction, governing formation of the transmembrane {beta}-hairpins (TMH) in the pore state of Ply, which can be extended to other CDCs. H150 in Ply-NH disrupts this interaction, while I172 provides structural rigidity to domain-3, through hydrophobic interactions, inhibiting TMH formation. Loss of pore forming activity enabled improved cellular invasion and autophagy evasion, promoting an atypical intracellular lifestyle for pneumococcus, a finding that was corroborated in in vivo infection models. Attenuation of inflammatory responses and tissue damage promoted tolerance of Ply-NH-expressing pneumococcus in the lower respiratory tract. Adoption of this altered lifestyle may be necessary for ST306 due to its limited nasopharyngeal carriage, with loss of pore forming ability of Ply facilitating a benign association of SPN in an alternative, intracellular host niche. AUTHOR SUMMARYStreptococcus pneumoniae, the main causative agent of pneumonia, triggers inflammation and tissue damage by expressing a pore-forming toxin, pneumolysin (Ply). Ply-induced inflammation drives pneumococcal transmission from nasopharynx (its primary reservoir), but also contributes to host mortality, limiting its occupiable habitats. Here, we uncovered the structural basis for loss of pore-forming activity of a Ply variant, present in Serotype 1 ST306, and observed that this enabled adoption of an intracellular lifestyle, attenuating inflammatory responses and prolonging host tolerance of pneumococcus in the lower airways. This commensal-like lifestyle, resembling that of members of the mitis group of Streptococci, might have evolved within ST306 by loss of function ply mutations, compensating for limited nasopharyngeal carriage capacity by facilitating adaptation to an alternate niche.

microbiology↗