The ParABS system is composed of three components: a centromeric sequence, parS, and two proteins, the ParA (ATPase) and the ParB DNA binding proteins. Hundreds of ParB proteins assemble dynamically to form nucleoprotein parS-anchored complexes (ParBS) that serve as substrates for ParA molecules to catalyze positioning and segregation events. We address the theoretical modeling of ParBS with a Lattice Gas models and compare it to experiments [1]. We give evidences that (i) ParBS is formed via a Liquid-Liquid Phase Separation in the metastable region of the phase diagram and (ii) this nucleation is catalyzed with the parS sequence [1].[1] Guilhas, Walter,... & Nollmann (2020). ATP-driven separation of liquid phase condensates in bacteria. Mol. Cell, 79, 293-303.

Recently T. Bridgeland defined a complex hyperk\"ahler metric on the tangent bundle over the space of stability conditions of a triangulated category, based on a Riemann-Hilbert problem determined by the Donaldson-Thomas invariants. This metric is encoded in a function $W(z,\theta)$ satisfying a heavenly equation, or a potential $F(z,\theta)$ satisfying an isomonodromy equation. After recasting the RH problem into a system of TBA-type equations, we obtain integral expressions for both $W$ and $F$ in terms of solutions of that system. These expressions are recognized as conformal limits of the `instanton generating potential' and `contact potential' appearing in studies of D-instantons and BPS black holes. By solving the TBA equations iteratively, we reproduce Joyce's original construction of $F$ as a formal series in the rational DT invariants. Furthermore, we produce similar solutions to deformed versions of the heavenly and isomonodromy equations involving a non-commutative star-product. In the case of a finite uncoupled BPS structure, we rederive the results previously obtained by Bridgeland and obtain the so-called $\tau$ function for arbitrary values of the fiber coordinates $\theta$, in terms of a suitable two-variable generalization of Barnes' $G$ function.

ParAB S , the most widespread bacterial DNA segregation system, is composed of a centromeric sequence, parS , and two proteins, the ParA ATPase and the ParB DNA binding proteins. Hundreds of ParB proteins assemble dynamically to form nucleoprotein parS -anchored complexes that serve as substrates for ParA molecules to catalyze positioning and segregation events. The exact nature of this ParB S complex has remained elusive, what we address here by revisiting the Stochastic Binding model (SBM) introduced to explain the non-specific binding profile of ParB in the vicinity of parS . In the SBM, DNA loops stochastically bring loci inside a sharp cluster of ParB. However, previous SBM versions did not include the negative supercoiling of bacterial DNA, leading to use unphysically small DNA persistences to explain the ParB binding profiles. In addition, recent super-resolution microscopy experiments have revealed a ParB cluster that is significantly smaller than previous estimations and suggest that it results from a liquid-liquid like phase separation. Here, by simulating the folding of long (≥ 30 kb) supercoiled DNA molecules calibrated with realistic DNA parameters and by considering different possibilities for the physics of the ParB cluster assembly, we show that the SBM can quantitatively explain the ChIP-seq ParB binding profiles without any fitting parameter, aside from the supercoiling density of DNA, which, remarkably, is in accord with independent measurements. We also predict that ParB assembly results from a non-equilibrium, stationary balance between an influx of produced proteins and an outflux of excess proteins, i.e., ParB clusters behave like liquid-like protein condensates with unconventional “leaky” boundaries.

With their potent regenerative and protective capacities, stem cell-derived conditioned media emerged as an effective alternative to cell therapy, and have a prospect to be manufactured as pharmaceutical products for tissue regeneration applications. Our study investigates the neuroregenerative potential of human dental pulp cells (DPCs) conditioned medium (CM) and defines an optimization strategy of DPC-CM for enhanced neuronal outgrowth. Primary sensory neurons from mouse dorsal root ganglia were cultured with or without DPC-CM, and the lengths of βIII-tubulin positive neurites were measured. The impacts of several manufacturing features as the duration of cell conditioning, CM storage, and preconditioning of DPCs with some factors on CM functional activity were assessed on neurite length. We observed that DPC-CM significantly enhanced neurites outgrowth of sensory neurons in a concentration-dependent manner. The frozen storage of DPC-CM had no impact on experimental outcomes and 48 h of DPC conditioning is optimal for an effective activity of CM. To further understand the regenerative feature of DPC-CM, we studied DPC secretome by human growth factor antibody array analysis and revealed the presence of several factors involved in either neurogenesis, neuroprotection, angiogenesis, and osteogenesis. The conditioning of DPCs with the B-27 supplement enhanced significantly the neuroregenerative effect of their secretome by changing its composition in growth factors. Here, we show that DPC-CM significantly stimulate neurite outgrowth in primary sensory neurons. Moreover, we identified secreted protein candidates that can potentially promote this promising regenerative feature of DPC-CM.

Minimal varying $\Lambda$ theories are defined by an action built from the Einstein-Cartan-Holst first order action for gravity with the cosmological constant $\Lambda$ as an independent scalar field, and supplemented by the Euler and Pontryagin densities multiplied by $1/\Lambda$. We identify the canonical structure of these theories which turn out to represent an example of irregular systems. We find five degrees of freedom on generic backgrounds and for generic values of parameters, whereas if the parameters satisfy a certain condition (which includes the most commonly considered Euler case) only three degrees of freedom remain. On de Sitter-like backgrounds the canonical structure changes, and due to an emergent conformal symmetry one degree of freedom drops from the spectrum. We also analyze the self-dual case with an holomorphic action depending only on the self-dual part of the connection. In this case we find two (complex) degrees of freedom, and further discuss the Kodama state, the restriction to de Sitter background and the effect of reality conditions.