Impact of Deuteration and Temperature on Furan Ring Dynamics

Despite significant progress in conformational analysis of cyclic molecules, the number of computational studies is still limited while most of that available in the literature data have been obtained long time ago with outdated methods. In present research, we have studied temperature driven conformational changes of the furan ring at three different temperatures. Additionally, the effect of deuteration on the ring dynamics is discussed; in addition, the aromaticity indices following the Bird and HOMA schemes are computed along all trajectories. Our ab initio molecular dynamic simulations revealed that deuteration has changed the furan ring dynamics and the obvious consequences; in addition, the shape and size of molecule are expected to be different.

Progression of the late-stage divisome is unaffected by the depletion of the cytoplasmic FtsZ pool

Cell division is a central and essential process in most bacteria, and also due to its complexity and highly coordinated nature, it has emerged as a promising new antibiotic target pathway in recent years. We have previously shown that ADEP antibiotics preferably induce the degradation of the major cell division protein FtsZ, thereby primarily leading to a depletion of the cytoplasmic FtsZ pool that is needed for treadmilling FtsZ rings. To further investigate the physiological consequences of ADEP treatment, we here studied the effect of ADEP on the different stages of the FtsZ ring in rod-shaped bacteria. Our data reveal the disintegration of early FtsZ rings during ADEP treatment in Bacillus subtilis, indicating an essential role of the cytoplasmic FtsZ pool and thus FtsZ ring dynamics during initiation and maturation of the divisome. However, progressed FtsZ rings finalized cytokinesis once the septal peptidoglycan synthase PBP2b, a late-stage cell division protein, colocalized at the division site, thus implying that the concentration of the cytoplasmic FtsZ pool and FtsZ ring dynamics are less critical during the late stages of divisome assembly and progression.

Ring dynamics around the Centaur Chariklo and the dwarf planet Haumea: effects of high-order resonances

<p>Narrow and dense rings have been detected around the small Centaur body Chariklo (Braga-Ribas et al. 2014), as well as around the dwarf planet Haumea (Ortiz et al. 2017).</p> <p>Both objects have non-axisymmetric shapes that induce strong resonant effects between the rotating central body with spin rate <em>Ω </em>and the radial epicyclic motion of the ring particles, <em>κ</em>. These resonances include the classical Eccentric Lindblad Resonances (ELR), where <em>κ = m(n-Ω),</em> with <em>m</em> integer, <em>n </em>being the particle mean motion. These resonances create an exchange of angular momentum between the body and the collisional ring, clearing the corotation zone, pushing the inner disk onto the body and repelling the outer part outside of the outermost 1/2 ELR, where the particles complete one orbital revolution while the body executes two rotations, i.e. <em>n/Ω ~ </em>1/2 (Sicardy et al. 2019)</p> <p>Here I will focus on higher-order resonances. They may appear either by considering other resonances such as <em>n/Ω ~ </em>1/3, or the same resonance as above (<em>n/Ω ~ </em>1/2), but with a body that has a triaxial shape. In this case, the invariance of the potential under a rotation of<em> π</em> radians transforms the 1st-order 1/2 Lindblad Resonance into a 2nd order 2/4 resonance.</p> <p>Second-order resonances are of particular interest because they force a strong response of the particles near the resonance radius, in spite of the intrinsically small strength of their forcing terms. This stems from the topography of the associated resonant Hamiltonian, which possesses an unstable hyperbolic point at its origin.</p> <p>The width of the region where this strong response is expected will be discussed for both Chariklo's and Haumea's rings. The special case of the second-order 1/3 resonance will be discussed, as it appears that both ring systems are close to that resonance.</p> <p>This work is intended, among others, to pave the way for future collisional simulations of rings around non-axisymmetric bodies.</p> <div class="page" title="Page 1"> <div class="layoutArea"> <div class="column"> <p>Braga-Ribas et al., 2014, <em>Nature</em> <strong>508</strong>, 72<br />Ortiz et al., 2017, <em>Nature</em> <strong>550</strong>, 219<br />Sicardy et al., 2019, <em>Nature Astronomy</em> <strong>3</strong>, 146</p> <p>The work leading to these results has received funding from the European Research Council under the European Community's H2020 2014-2020 ERC Grant Agreement n°669416 "Lucky Star"</p> </div> </div> </div>

Mitochondrial morphology and activity regulate furrow ingression and contractile ring dynamics in Drosophila cellularization

Drp1-regulated mitochondrial fission is essential for mitochondrial distribution across the cell in cellularization during Drosophila embryogenesis. Loss of mitochondrial fission in Drp1 mutant embryos leads to defects in morphogenetic events of cell formation and contractile ring constriction in cellularization.

Selectively Compliant Annuloplasty Ring to Enable Annular Dynamics in Mitral Valve Repair Evaluated by In-Vitro Stereovision

Mitral valve (MV) annular dynamics are critical to the long term efficacy of MV repair. Today’s annuloplasty rings, used to restore MV function, impose significant constraints on the motion profile of the MV annulus. We present a selectively compliant ring that provides sufficient stiffness to stabilize a diseased annulus while allowing physiological annular dynamics. Ring design is informed by a finite element analysis and experimentally evaluated with in-vitro stereophotogrammetry. We compare the ring dynamics to commercially available semi-rigid rings as well as values found in literature for healthy annuli. The results demonstrate that motion of the selectively compliant ring is significantly closer to that of a healthy annulus based on standard metrics that define MV annular movement. Specifically, the metrics for the new ring compare to those in literature as follows: change in orifice area 12.5 ± 3% vs.10 ± 2%; change in anterior-posterior diam. 5.4 ± 0.3% vs. 7 ± 1%; change in inter-commissural diam. 6.6 ± 1.3% vs. 5 ± 1%.

Inhibiting Mycobacterium tuberculosis ClpP1P2 by addressing the equatorial handle domain of ClpP1 subunit

Unlike other bacterial ClpP systems, mycobacterial ClpP1P2 complex is essential for mycobacterial survival. The functional details of Mycobacterium tuberculosis (Mtb) ClpP1P2 remains largely elusive and selectively targeting ClpP of different species is a big challenge. In this work, cediranib was demonstrated to significantly decrease the activity of MtbClpP1P2. By solving the crystal structure of cediranib-bound MtbClpP1P2, we found that cediranib dysregulates MtbClpP1P2 by interfering with handle domain of the equatorial region of MtbClpP1, indicating that the inter-ring dynamics are crucial for its function. This finding provides direct evidence for the notion that a conformational switch in the equatorial handle domain is essential for ClpP activity. We also present biochemical data to interpret the distinct interaction pattern and inhibitory properties of cediranib toward MtbClpP1P2. These results suggest that the variable handle domain region is responsible for the species-selectivity of cediranib, which suggests the equatorial handle domain as a potential region for screening pathogen-specific ClpP inhibitors.