Coronin 1B supports RhoA signaling at cell-cell junctions through Myosin II

Non-muscle myosin II (NMII) motor proteins are responsible for generating contractile forces inside eukaryotic cells. There is also a growing interest in the capacity for these motor proteins to influence cell signaling through scaffolding, especially in the context of RhoA GTPase signaling. We previously showed that NMIIA accumulation and stability within specific regions of the cell cortex, such as the zonula adherens (ZA), allows the formation of a stable RhoA signaling zone. Now we demonstrate a key role for Coronin 1B in maintaining this junctional pool of NMIIA, as depletion of Coronin 1B significantly compromised myosin accumulation and stability at junctions. The loss of junctional NMIIA, upon Coronin 1B knockdown, perturbed RhoA signaling due to enhanced junctional recruitment of the RhoA antagonist, p190B Rho GAP. This effect was blocked by the expression of phosphomimetic MRLC-DD, thus reinforcing the central role of NMII in regulating RhoA signaling.     

A life‐history perspective on the demographic drivers of structured population dynamics in changing environments

Current understanding of life‐history evolution and how demographic parameters contribute to population dynamics across species is largely based on assumptions of either constant environments or stationary environmental variation. Meanwhile, species are faced with non‐stationary environmental conditions (changing mean, variance, or both) created by climate and landscape change. To close the gap between contemporary reality and demographic theory, we develop a set of transient life table response experiments (LTREs) for decomposing realised population growth rates into contributions from specific vital rates and components of population structure. Using transient LTREs in a theoretical framework, we reveal that established concepts in population biology will require revision because of reliance on approaches that do not address the influence of unstable population structure on population growth and mean fitness. Going forward, transient LTREs will enhance understanding of demography and improve the explanatory power of models used to understand ecological and evolutionary dynamics.     

Binding of FANCI-FANCD2 Complex to RNA and R-Loops Stimulates Robust FANCD2 Monoubiquitination

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Computational study of enantioselective interaction between C<Subscript>60</Subscript> fullerene and its derivatives with L-histidine

The mechanism of the enantioselective binding of L-histidine with C₆₀ fullerene and its derivatives, (1,2-methanofullerene C₆₀)-61-carboxylic acid, diethyl (1,2-methanofullerene C₆₀)-61-61-dicarboxylate and tert-butyl (1,2-methanofullerene C₆₀)-61-carboxylate based chiral selectors was studied by quantum chemical calculations. All the molecules were fully optimized at RHF/6-31G* basis set. Relative energies between the different complexes were subsequently estimated with single-point electronic energies computed using Møller-Plesset perturbation theory (MP2). Stability and feasibility of all the generated structures were supported by their respective energy minima and fundamental frequencies. It was observed that interaction of fullerene derivatives with L-histidine is due to the existence of hydrogen bonding forces during the complex formation. The intermolecular forces, flow of atomic charges, binding energy, hardness, dipole moment and localization of electrostatic potential are in agreement with enantioselective interaction of L-histidine with C₆₀ fullerene and its derivatives. It is found that theoretical evaluation to be consistent with the experimental data.     

Pitfalls to avoid in nonlinear perturbation analysis of structured population models

Despite the ubiquity of nonlinear functional relationships in nature we tend to characterize mechanisms in science using more tractable linear functions. In demographic modeling, transfer function analysis is used to calculate the nonlinear response of population growth rate to a theoretical perturbation of one or more matrix elements. This elegant approach is not yet popular in ecology. Inconveniently, using transfer function without care can produce erroneous results without warning. We used a large matrix projection model database to explore the potential pitfalls to be avoided in using transfer function analysis. We asked a fundamental population control question, what matrix element perturbation would be needed to reach a minimum goal of replacement population growth? We then tracked instances in which transfer function yields erroneous output and explored these cases in detail to measure how frequently it occurs. We developed a phylogenetically-corrected mixed effects logistic regression model in a Bayesian framework to test the effect of species traits and the identity of matrix elements on the probability that transfer function yields errors. We found in 16% of cases the transfer function yielded erroneous outcomes. These errors were more likely when perturbing demographic stasis and also for shrubs more than any other life form. Errors in transfer function analysis were often due to perturbing matrix elements beyond their biological limits, even when this is still mathematically correct. To use transfer function analysis properly in demographic modeling and avoid erroneous results, input must be carefully selected to include only a biologically admissible set of perturbations.     

Walking through the looking glass: Adapting gait patterns with mirror feedback

Clinical locomotor research seeks to facilitate adaptation or retention of new walking patterns by providing feedback. Within a split-belt treadmill paradigm, sagittal plane feedback improves adaptation but does not affect retention. Representation of error in this manner is cognitively demanding. However, it is unknown in this paradigm how frontal plane feedback, which may utilize a unique learning process, impacts locomotor adaptation. Frontal plane movement feedback has been shown to impact retention of novel running mechanics but has yet to be evaluated in gait conditions widely applicable within neurorehabilitation, such as walking. The purpose of this study was to investigate the effects of frontal plane mirror feedback on gait adaptation and retention during split-belt treadmill walking. Forty healthy young adults were divided into two groups: one group received mirror feedback during the first split-belt exposure and the other received no mirror feedback. Individuals in the mirror feedback group were asked to look at their legs in the mirror, but no further instructions were given. Individuals with mirror feedback displayed more symmetric stance time during the first strides of adaptation and maintained this pattern into the second split-belt exposure when no feedback was provided. Individuals with mirror feedback also demonstrated more symmetric double support time upon returning to normal walking. Lastly, the mirror feedback also allowed individuals to walk with smaller gait variability during the final steps of both split-belt exposures. Overall, mirror feedback allowed individuals to reduce their stance time asymmetry and led to a more consistent adapted pattern, suggesting this type of feedback may have utility in gait training that targets symmetry and consistency in movement.     

Identification of human plasma C1 inhibitor as a target protein for staphylococcal superantigen-like protein 5 (SSL5)

The family of staphylococcal superantigen-like proteins (SSLs) have a structure similar to bacterial superantigens but exhibit no superantigenic activity. These exoproteins have recently been shown to disturb the host immune defense system. One family member, SSL5, was reported to bind to human leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) and matrix metalloproteinase-9 (MMP-9) and to interfere with leukocyte trafficking. In the present study, we explored human plasma proteins bound by glutathione S-transferase (GST)-tagged recombinant SSL5 (GST-SSL5) and identified plasma protease C1 inhibitor (C1Inh) as a major SSL5-binding protein based on the results of peptide mass fingerprinting analysis with MALDI-TOFMS. GST-SSL5 was found to attenuate the inhibitory activity of recombinant histidine-tagged C1Inh (C1Inh-His) toward complement C1s. We also observed that the treatment of C1Inh-His with neuraminidase markedly decreased its binding to GST-SSL5. Moreover, C1Inh-His produced by Lec2 mutant cells (deficient in sialic acid biosynthesis) showed much lower binding affinity for SSL5 than that produced by the wild-type CHO-K1 cells, as assessed by pull-down assay. These results suggest that SSL5 binds to C1Inh in a sialic acid-dependent fashion and modulates the host immune defense through perturbation of the complement system in association with S. aureus infection.