WBS: Weighted Backtracking Strategy for Symbolic Testing of Embedded Software

Suresh, Varsha P; Chakrabarti, Sujit Kumar; Suresh, Athul; Jetley, Raoul

doi:10.18293/seke2022-147

Cited by 2 publications

(2 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis was carried out using custom scripts written in python ( https://github.com/p-sur/Myddosome-localisation ; copy archived at Suresh, 2024 ). Cell boundaries and centroid coordinates were extracted from the acquired xyzt hyperstacks.…”

Section: Methodsmentioning

confidence: 99%

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide

Li,

Suresh,

Brelstaff

et al. 2024

eLife

View full text Add to dashboard Cite

The Myddosome is a key innate immune signalling platform. It forms at the cell surface and contains MyD88 and IRAK proteins which ultimately coordinate the production of pro-inflammatory cytokines. Toll-like receptor 4 signals via the Myddosome when triggered by Lipopolysaccharide (LPS) or Amyloid-Beta (Aβ) aggregates but the magnitude and time duration of the response are very different for reasons that are unclear. Here we followed the formation of Myddosomes in live macrophages using local delivery of TLR4 agonist to the cell surface and visualisation with 3D rapid light sheet imaging. This was complemented by super-resolution imaging of Myddosomes in fixed macrophages to determine the size of the signalling complex at different times after triggering. Myddosomes formed more rapidly after LPS than in response to sonicated Aβ 1-42 fibrils (80 seconds vs 372 seconds). The mean lifetimes of the Myddosomes was also shorter when triggered by LPS compared to sonicated Aβ fibrils (170 and 220 s) respectively. In both cases a range of Myddosome of different sizes (50-500 nm) were formed. In particular, small round Myddosomes around 100 nm in size formed at early time points, then reduced in proportion over time. Collectively our data suggests that compared to LPS the multivalency of Aβ fibrils leads to the formation of larger Myddosomes which form more slowly and, due to their size, take longer to disassemble. This explains why sonicated Aβ fibrils results in less efficient triggering of TLR4 signalling and may be a general property of protein aggregates.

show abstract

Section: Methodsmentioning

confidence: 99%

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide

Li,

Suresh,

Brelstaff

et al. 2024

eLife

View full text Add to dashboard Cite

show abstract

“…Source code for the model developed and used in this work can be found on Github ( https://github.com/RPGroup-PBoC/kfiber_modeling_manipulation , Suresh, 2022 copy archived at swh:1:rev:dee771a47e82df5fb88c25cfc777ba377f8bb234 ). We adopt the Euler-Bernoulli formalism as a framework to model how k-fibers bend elastically in response to force ( Gittes et al, 1993 ; Brangwynne et al, 2006 ; Jiang and Zhang, 2008 ).…”

Section: Methodsmentioning

confidence: 99%

Modeling and mechanical perturbations reveal how spatially regulated anchorage gives rise to spatially distinct mechanics across the mammalian spindle

Suresh

Galstyan

Phillips

et al. 2022

eLife

View full text Add to dashboard Cite

During cell division, the spindle generates force to move chromosomes. In mammals, microtubule bundles called kinetochore-fibers (k-fibers) attach to and segregate chromosomes. To do so, k-fibers must be robustly anchored to the dynamic spindle. We previously developed microneedle manipulation to mechanically challenge k-fiber anchorage, and observed spatially distinct response features revealing the presence of heterogeneous anchorage (Suresh et al., 2020). How anchorage is precisely spatially regulated, and what forces are necessary and sufficient to recapitulate the k-fiber’s response to force remain unclear. Here, we develop a coarse-grained k-fiber model and combine with manipulation experiments to infer underlying anchorage using shape analysis. By systematically testing different anchorage schemes, we find that forces solely at k-fiber ends are sufficient to recapitulate unmanipulated k-fiber shapes, but not manipulated ones for which lateral anchorage over a 3 μm length scale near chromosomes is also essential. Such anchorage robustly preserves k-fiber orientation near chromosomes while allowing pivoting around poles. Anchorage over a shorter length scale cannot robustly restrict pivoting near chromosomes, while anchorage throughout the spindle obstructs pivoting at poles. Together, this work reveals how spatially regulated anchorage gives rise to spatially distinct mechanics in the mammalian spindle, which we propose are key for function.

show abstract

WBS: Weighted Backtracking Strategy for Symbolic Testing of Embedded Software

Cited by 2 publications

References 8 publications

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide

The delayed kinetics of Myddosome formation explains why amyloid-beta aggregates trigger Toll-like receptor 4 less efficiently than lipopolysaccharide

Modeling and mechanical perturbations reveal how spatially regulated anchorage gives rise to spatially distinct mechanics across the mammalian spindle

Contact Info

Product

Resources

About