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Lacroix Roman posted an update 6 months, 3 weeks ago
Our data uncover the uncharacterized functions of DIAPH3 and provide evidence that this protein belongs to a molecular toolbox that links microtubule dynamics during mitosis to aneuploidy, cell death, fate determination defects, and cortical malformation.New mathematical model reveals how the flagella of some single-celled algae generate a lasso-like beat pattern that propels the cell through water.Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties of V1R during early embryonic development of the mouse spinal cord locomotor networks (E11.5-E16.5). We found that these interneurons are subdivided into several functional clusters from E11.5 and then display an unexpected transitory involution process during which they lose their ability to sustain tonic firing. We demonstrated that the essential factor controlling the diversity of the discharge pattern of embryonic V1R is the ratio of a persistent sodium conductance to a delayed rectifier potassium conductance. Taken together, our results reveal how a simple mechanism, based on the synergy of two voltage-dependent conductances that are ubiquitous in neurons, can produce functional diversity in embryonic V1R and control their early developmental trajectory.We propose and discuss a model for flagellar mechanics in Euglena gracilis. We show that the peculiar non-planar shapes of its beating flagellum, dubbed ‘spinning lasso’, arise from the mechanical interactions between two of its inner components, namely, the axoneme and the paraflagellar rod. The spontaneous shape of the axoneme and the resting shape of the paraflagellar rod are incompatible. Thus, the complex non-planar configurations of the coupled system emerge as the energetically optimal compromise between the two antagonistic components. The model is able to reproduce the experimentally observed flagellar beats and the characteristic geometric signature of spinning lasso, namely, traveling waves of torsion with alternating sign along the length of the flagellum.Recent genetic data can offer important insights into the roles of lipoprotein subfractions and particle sizes in preventing coronary artery disease (CAD), as previous observational studies have often reported conflicting results. We used the LD score regression to estimate the genetic correlation of 77 subfraction traits with traditional lipid profile and identified 27 traits that may represent distinct genetic mechanisms. We then used Mendelian randomization (MR) to estimate the causal effect of these traits on the risk of CAD. #link# In univariable MR, the concentration and content of medium high-density lipoprotein (HDL) particles showed a protective effect against CAD. The effect was not attenuated in multivariable analyses. Multivariable MR analyses also found that small HDL particles and smaller mean HDL particle diameter may have a protective effect. We identified four genetic markers for HDL particle size and CAD. Further investigations are needed to fully understand the role of HDL particle size.Translation-dependent quality control pathways such as no-go decay (NGD), non-stop decay (NSD), and nonsense-mediated decay (NMD) govern protein synthesis and proteostasis by resolving non-translating ribosomes and preventing the production of potentially toxic peptides derived from faulty and aberrant mRNAs. However, how translation is altered and the in vivo defects that arise in the absence of these pathways are poorly understood. Here, we show that the NGD/NSD factors Pelo and Hbs1l are critical in mice for cerebellar neurogenesis but expendable for survival of these neurons after development. Enpp-1-IN-1 molecular weight of mutant mouse embryonic fibroblasts revealed translational pauses, alteration of signaling pathways, and translational reprogramming. Similar effects on signaling pathways, including mTOR activation, the translatome and mouse cerebellar development were observed upon deletion of the NMD factor Upf2. Our data reveal that these quality control pathways that function to mitigate errors at distinct steps in translation can evoke similar cellular responses.The diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells generate different numbers of polarity sites. Mass-conserved activator-substrate (MCAS) models that describe polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. Theoretical analyses predicted that competition would slow dramatically as GTPase concentrations at different polarity sites increase toward a ‘saturation point’, allowing polarity sites to coexist. Here, we test this prediction using budding yeast cells, and confirm that increasing the amount of key polarity proteins results in multiple polarity sites and simultaneous budding. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells with diverse morphologies may determine the number of polarity sites.Everyday financial behaviour involves inter-temporal choices, between saving, spending, and debt. Consumers do not always take these decisions to their best advantage. Ainslie’s analysis of the means to willpower as suppression, resolve, and habit is potentially applicable to understanding and improving the decisions that consumers make. Some relevant research on these topics exists, and it is briefly reviewed here.Ainslie’s account of willpower addresses many important mechanisms (e.g., habit, visceral activation, and implementation intention). We argue that a model of willpower should be grounded in general psychological principles and with a primary focus on their interplay. We discuss the reflective-impulsive model that covers willpower and impulsiveness as special constellations of processes that govern various forms of cognition and behavior.
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