scholarly journals The loader complex Scc2/4 forms co-condensates with DNA as loading sites for cohesin

2021 ◽  
Author(s):  
Sarah Zernia ◽  
Dieter Kamp ◽  
Johannes Stigler
Keyword(s):  
Phase Separation ◽  
Optical Tweezer ◽  
Cohesin Complex ◽  
Droplet Shape ◽  
Nucleosome Formation ◽  
Starting Point ◽  
Chromatid Cohesion ◽  
The Stability ◽  
Protein Recruitment ◽  
Condensed Dna

The genome is organized by diverse packaging mechanisms like nucleosome formation, loop extrusion and phase separation, which all compact DNA in a dynamic manner. Phase separation additionally drives protein recruitment to condensed DNA sites and thus regulates gene transcription. The cohesin complex is a key player in chromosomal organization that extrudes loops to connect distant regions of the genome and ensures sister chromatid cohesion after S-phase. For stable loading onto the DNA and for activation, cohesin requires the loading complex Scc2/4. As the precise loading mechanism remains unclear, we investigated whether phase separation might be the initializer of the cohesin recruitment process. We found that, in absence of cohesin, budding yeast Scc2/4 forms phase separated co-condensates with DNA, which comprise liquid-like properties shown by droplet shape, fusion ability and reversibility. We reveal in DNA curtain and optical tweezer experiments that these condensates are built by DNA bridging and bending through Scc2/4. Importantly, Scc2/4-mediated condensates recruit cohesin efficiently and increase the stability of the cohesin complex. We conclude that phase separation properties of Scc2/4 enhance cohesin loading by molecular crowding, which might then provide a starting point for the recruitment of additional factors and proteins.

COO vs ROO: importance of the origin in customer preferences towards financial entities

2017 ◽  
Vol 34 (2) ◽  
pp. 206-223 ◽  
Author(s):  
José Manuel García-Gallego ◽  
Antonio Chamorro Mera
Keyword(s):  
Brand Management ◽  
Preference Structure ◽  
Content Type ◽  
Services Sector ◽  
Customer Preferences ◽  
Starting Point ◽  
Remarkable Result ◽  
Place Of Origin ◽  
Regional Brand ◽  
The Stability

Purpose The purpose of this paper is to determine the importance that customers give to the origin attribute when selecting a financial entity compared to other features directly related to the service that these institutions provide. In addition, this study aims at analysing what level of brand origin provides a greater utility for customers in their preference structure: regional, national or foreign. Design/methodology/approach The technique of conjoint analysis is applied via a survey of 427 customers to determine customers’ preference structure when choosing a financial entity. Findings Of particular note among the main results is the great importance the respondents give to the origin of the entity, preferring regional over national or foreign institutions. The existence of three different segments of customers based on their preference structure is also a remarkable result. Research limitations/implications Place-of-origin effect is not universal. Due to this fact, the results of the studies focussed on this research topic are difficult to extrapolate to other geographical areas. Practical implications The current situation in southern Europe financial sector obliges many small financial entities to undertake mergers in order to face the stability and solvency policies established by European Central Bank. In this sense, these institutions must decide whether or not to maintain their regional brand identity. The results of this study show the appropriateness of maintaining and communicating the regional origin of the entities. These findings will contribute to guiding decision making on brand management for financial entities. Originality/value To the best of the knowledge, there is a lack of research on the place-of-origin through different levels simultaneously. This paper provides a starting point for further research about this effect in the services sector.

scholarly journals Simulation of FUS protein condensates with an adapted coarse-grained model

2020 ◽  
Author(s):  
Zakarya Benayad ◽  
Sören von Bülow ◽  
Lukas S. Stelzl ◽  
Gerhard Hummer
Keyword(s):  
Free Energy ◽  
Phase Separation ◽  
Potential Energy ◽  
Energy Function ◽  
Potential Energy Function ◽  
Scaling Factor ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
General Strategy ◽  
Droplet Shape

AbstractDisordered proteins and nucleic acids can condense into droplets that resemble the membraneless organelles observed in living cells. MD simulations offer a unique tool to characterize the molecular interactions governing the formation of these biomolecular condensates, their physico-chemical properties, and the factors controlling their composition and size. However, biopolymer condensation depends sensitively on the balance between different energetic and entropic contributions. Here, we develop a general strategy to fine-tune the potential energy function for molecular dynamics simulations of biopolymer phase separation. We rebalance protein-protein interactions against solvation and entropic contributions to match the excess free energy of transferring proteins between dilute solution and condensate. We illustrate this formalism by simulating liquid droplet formation of the FUS low complexity domain (LCD) with a rebalanced MARTINI model. By scaling the strength of the nonbonded interactions in the coarse-grained MARTINI potential energy function, we map out a phase diagram in the plane of protein concentration and interaction strength. Above a critical scaling factor of αc ≈ 0.6, FUS LCD condensation is observed, where α = 1 and 0 correspond to full and repulsive interactions in the MARTINI model, respectively. For a scaling factor α = 0.65, we recover the experimental densities of the dilute and dense phases, and thus the excess protein transfer free energy into the droplet and the saturation concentration where FUS LCD condenses. In the region of phase separation, we simulate FUS LCD droplets of four different sizes in stable equilibrium with the dilute phase and slabs of condensed FUS LCD for tens of microseconds, and over one millisecond in aggregate. We determine surface tensions in the range of 0.01 to 0.4mN/m from the fluctuations of the droplet shape and from the capillary-wave-like broadening of the interface between the two phases. From the dynamics of the protein end-to-end distance, we estimate shear viscosities from 0.001 to 0.02Pas for the FUS LCD droplets with scaling factors α in the range of 0.625 to 0.75, where we observe liquid droplets. Significant hydration of the interior of the droplets keeps the proteins mobile and the droplets fluid.

scholarly journals Absence of the Spindle Assembly Checkpoint restores mitotic fidelity upon loss of sister chromatid cohesion

2018 ◽  
Author(s):  
Rui D. Silva ◽  
Mihailo Mirkovic ◽  
Leonardo G. Guilgur ◽  
Om S. Rathore ◽  
Rui Gonçalo Martinho ◽  
...  
Keyword(s):  
Cell Survival ◽  
Sister Chromatid ◽  
Spindle Assembly Checkpoint ◽  
Genome Shuffling ◽  
Spindle Assembly ◽  
Sister Chromatid Cohesion ◽  
Abnormal Development ◽  
Wing Development ◽  
Cohesin Complex ◽  
Chromatid Cohesion

AbstractSister chromatid cohesion is essential for faithful mitosis, as premature cohesion loss leads to random chromosome segregation and aneuploidy, resulting in abnormal development. To identify specific conditions capable of restoring defects associated with cohesion loss, we screened for genes whose depletion modulates Drosophila wing development when sister chromatid cohesion is impaired. Cohesion deficiency was induced by knock-down of the acetyltransferase Separation anxiety (San)/Naa50, a cohesin complex stabilizer. Several genes whose function impacts wing development upon cohesion loss were identified. Surprisingly, knockdown of key Spindle Assembly Checkpoint (SAC) proteins, Mad2 and Mps1, suppressed developmental defects associated with San depletion. SAC impairment upon cohesin removal, triggered by San depletion or artificial removal of the cohesin complex, prevented extensive genome shuffling, reduced segregation defects and restored cell survival. This counterintuitive phenotypic suppression was caused by an intrinsic bias for efficient chromosome bi-orientation at mitotic entry, coupled with slow engagement of error-correction reactions. We conclude that mitotic timing determines the severity of defects associated with cohesion deficiency. Therefore, although divisions are still error-prone, SAC inactivation enhances cell survival and tissue homeostasis upon cohesion loss.

scholarly journals Scc2/Nipbl hops between chromosomal cohesin rings after loading

2017 ◽  
Author(s):  
James D.P. Rhodes ◽  
Davide Mazza ◽  
Kim A. Nasmyth ◽  
Stephan Uphoff
Keyword(s):  
Single Molecule ◽  
Sister Chromatid ◽  
Fluorescence Recovery After Photobleaching ◽  
Sister Chromatid Cohesion ◽  
Dna Looping ◽  
Cohesin Complex ◽  
Single Molecule Tracking ◽  
Loading Function ◽  
Stop And Go ◽  
Chromatid Cohesion

AbstractThe cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping) via a process thought to involve entrapment of DNAs within its tripartite ring. It has been suggested that intra- chromosome loops are generated through processive extrusion of DNAs through the lumen of cohesin’s ring. Scc2 (Nipbl) is essential for loading cohesin onto chromosomes but not for maintaining sister chromatid cohesion following DNA replication. It has therefore been assumed that Scc2 is involved exclusively in the cohesin loading process. However, it is possible that the stimulation of cohesin’s ABC-like ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single-molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2’s movement within chromatin is consistent with a “stop-and-go” or “hopping” motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

Lyapunov-stable control of mechatronic systems

2005 ◽  
Vol 219 (2) ◽  
pp. 173-185 ◽  
Author(s):  
O Enge ◽  
P Maißer
Keyword(s):  
Inverse Dynamics ◽  
Dynamic Control ◽  
Linear Feedback ◽  
Mechatronic Systems ◽  
Electromechanical Systems ◽  
Starting Point ◽  
Reaction Forces ◽  
The Stability ◽  
Lagrange Formalism ◽  
Stable Control

In this paper, a method for controlling mechatronic systems using inverse dynamics is proposed. The starting point is a unified mathematical approach to modelling electromechanical systems based on Lagrange formalism. This mathematical theory is used to represent such systems taking into account all interactions between their substructures. The concept of Lagrange formalism for electromechanical systems is given and the complete governing equations are presented. The Voronetz equations of a partially kinematically controlled electromechanical system (EMS) are derived. The corresponding reaction forces and voltages following from the Voronetz equations are determined. Using these reactions with small modifications, a so-called ‘augmented proportional-derivative (PD) dynamic control law’ is generated. This controller consists of a non-linear feedforward - based on inverse dynamics - and a linear feedback. The stability of the controller is proved using a Lyapunov function. The controller can also be applied to pure multibody systems or a sheer electrical system, both of which are borderline cases of mechatronic systems.

scholarly journals An Accelerating Convergence Rate Method for Moving Morphable Components

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Ruichao Lian ◽  
Shikai Jing ◽  
Zhijun He ◽  
Zefang Shi ◽  
Guohua Song
Keyword(s):  
Convergence Rate ◽  
Three Dimensional ◽  
Structural Topology ◽  
Coarse Mesh ◽  
Starting Point ◽  
Good Starting Point ◽  
Topological Configuration ◽  
Rate Method ◽  
The Stability ◽  
Moving Morphable Components

In the structural topology optimization approaches, the Moving Morphable Components (MMC) is a new method to obtain the optimized structural topologies by optimizing shapes, sizes, and locations of components. However, the size of the mesh has a strong influence on the rate of which the component builds the initial topological configuration by moving. The influence may slow down the convergence rate. In this paper, a hierarchical mesh subdivision solution method that can accelerate the convergence rate for the MMC is developed. First, the coarse mesh is used as the starting point for the optimization problem, and the construction process of the initial topology structure is increased speed by accelerating the movement of components. Second, the optimized solution obtained by the coarse mesh is equivalently mapped to the same problem with a finer mesh and used to construct a good starting point for the next optimization. Finally, two-dimensional (2D) MBB beam example and three-dimensional (3D) short cantilever beam example are provided so as to validate that with the use of the proposed approach, demonstrating that this method can improve the convergence rate and the stability of the MMC method.

scholarly journals Analysis of the stability of 70 housekeeping genes during iPS reprogramming

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yulia Panina ◽  
Arno Germond ◽  
Tomonobu M. Watanabe
Keyword(s):  
Splice Variants ◽  
Expression Patterns ◽  
Housekeeping Genes ◽  
Ips Cells ◽  
Correlative Analysis ◽  
Neural Stem Cell Line ◽  
Genes Expression ◽  
Starting Point ◽  
Induced Pluripotent ◽  
The Stability

AbstractStudies on induced pluripotent stem (iPS) cells highly rely on the investigation of their gene expression which requires normalization by housekeeping genes. Whether the housekeeping genes are stable during the iPS reprogramming, a transition of cell state known to be associated with profound changes, has been overlooked. In this study we analyzed the expression patterns of the most comprehensive list to date of housekeeping genes during iPS reprogramming of a mouse neural stem cell line N31. Our results show that housekeeping genes’ expression fluctuates significantly during the iPS reprogramming. Clustering analysis shows that ribosomal genes’ expression is rising, while the expression of cell-specific genes, such as vimentin (Vim) or elastin (Eln), is decreasing. To ensure the robustness of the obtained data, we performed a correlative analysis of the genes. Overall, all 70 genes analyzed changed the expression more than two-fold during the reprogramming. The scale of this analysis, that takes into account 70 previously known and newly suggested genes, allowed us to choose the most stable of all genes. We highlight the fact of fluctuation of housekeeping genes during iPS reprogramming, and propose that, to ensure robustness of qPCR experiments in iPS cells, housekeeping genes should be used together in combination, and with a prior testing in a specific line used in each study. We suggest that the longest splice variants of Rpl13a, Rplp1 and Rps18 can be used as a starting point for such initial testing as the most stable candidates.

scholarly journals The cohesin complex regulates immunoglobulin class switch recombination

2013 ◽  
Vol 210 (12) ◽  
pp. 2495-2502 ◽  
Author(s):  
Anne-Sophie Thomas-Claudepierre ◽  
Ebe Schiavo ◽  
Vincent Heyer ◽  
Marjorie Fournier ◽  
Adeline Page ◽  
...  
Keyword(s):  
Cytidine Deaminase ◽  
Class Switch Recombination ◽  
Nonhomologous End Joining ◽  
Cohesin Complex ◽  
Dna Breaks ◽  
End Joining ◽  
Regulatory Subunits ◽  
Class Switch ◽  
Chromatid Cohesion ◽  
Switch Regions

Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to switch regions and by the subsequent generation of double-stranded DNA breaks (DSBs). These DNA breaks are ultimately resolved through the nonhomologous end joining (NHEJ) pathway. We show that during CSR, AID associates with subunits of cohesin, a complex previously implicated in sister chromatid cohesion, DNA repair, and the formation of DNA loops between enhancers and promoters. Furthermore, we implicate the cohesin complex in the mechanism of CSR by showing that cohesin is dynamically recruited to the Sμ-Cμ region of the IgH locus during CSR and that knockdown of cohesin or its regulatory subunits results in impaired CSR and increased usage of microhomology-based end joining.

scholarly journals Pds5p regulates the maintenance of sister chromatid cohesion and is sumoylated to promote the dissolution of cohesion

2003 ◽  
Vol 163 (4) ◽  
pp. 729-741 ◽  
Author(s):  
Kristen Stead ◽  
Cristina Aguilar ◽  
Theresa Hartman ◽  
Melissa Drexel ◽  
Pamela Meluh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Temperature Sensitivity ◽  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Cohesin Complex ◽  
Chromatid Cohesion ◽  
Chromosomal Loci

Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion.

scholarly journals Effect of density dependence on coinfection dynamics: part 2

2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Jonathan Andersson ◽  
Samia Ghersheen ◽  
Vladimir Kozlov ◽  
Vladimir G. Tkachev ◽  
Uno Wennergren
Keyword(s):  
Density Dependence ◽  
Equilibrium Points ◽  
Stable State ◽  
Positive Cone ◽  
Single Infection ◽  
Susceptible Population ◽  
Link Type ◽  
Starting Point ◽  
The Stability ◽  
Coexistence Equilibrium

AbstractIn this paper we continue the stability analysis of the model for coinfection with density dependent susceptible population introduced in Andersson et al. (Effect of density dependence on coinfection dynamics. arXiv:2008.09987, 2020). We consider the remaining parameter values left out from Andersson et al. (Effect of density dependence on coinfection dynamics. arXiv:2008.09987, 2020). We look for coexistence equilibrium points, their stability and dependence on the carrying capacity K. Two sets of parameter value are determined, each giving rise to different scenarios for the equilibrium branch parametrized by K. In both scenarios the branch includes coexistence points implying that both coinfection and single infection of both diseases can exist together in a stable state. There are no simple explicit expression for these equilibrium points and we will require a more delicate analysis of these points with a new bifurcation technique adapted to such epidemic related problems. The first scenario is described by the branch of stable equilibrium points which includes a continuum of coexistence points starting at a bifurcation equilibrium point with zero single infection strain #1 and finishing at another bifurcation point with zero single infection strain #2. In the second scenario the branch also includes a section of coexistence equilibrium points with the same type of starting point but the branch stays inside the positive cone after this. The coexistence equilibrium points are stable at the start of the section. It stays stable as long as the product of K and the rate $${\bar{\gamma }}$$ γ ¯ of coinfection resulting from two single infections is small but, after this it can reach a Hopf bifurcation and periodic orbits will appear.

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