TY - JOUR
AB - Inhibiting the histone H3–ASF1 (anti‐silencing function 1) protein–protein interaction (PPI) represents a potential approach for treating numerous cancers. As an α‐helix‐mediated PPI, constraining the key histone H3 helix (residues 118–135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3118–135 peptides bearing pentenylglycine residues at the i and i+4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that the potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy–entropy compensation occurs.
AU - Bakail, May M
AU - Rodriguez‐Marin, Silvia
AU - Hegedüs, Zsófia
AU - Perrin, Marie E.
AU - Ochsenbein, Françoise
AU - Wilson, Andrew J.
ID - 9016
IS - 7
JF - ChemBioChem
SN - 1439-4227
TI - Recognition of ASF1 by using hydrocarbon‐constrained peptides
VL - 20
ER -
TY - JOUR
AB - Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy.
AU - Bakail, May M
AU - Gaubert, Albane
AU - Andreani, Jessica
AU - Moal, Gwenaëlle
AU - Pinna, Guillaume
AU - Boyarchuk, Ekaterina
AU - Gaillard, Marie-Cécile
AU - Courbeyrette, Regis
AU - Mann, Carl
AU - Thuret, Jean-Yves
AU - Guichard, Bérengère
AU - Murciano, Brice
AU - Richet, Nicolas
AU - Poitou, Adeline
AU - Frederic, Claire
AU - Le Du, Marie-Hélène
AU - Agez, Morgane
AU - Roelants, Caroline
AU - Gurard-Levin, Zachary A.
AU - Almouzni, Geneviève
AU - Cherradi, Nadia
AU - Guerois, Raphael
AU - Ochsenbein, Françoise
ID - 9018
IS - 11
JF - Cell Chemical Biology
KW - Clinical Biochemistry
KW - Molecular Medicine
KW - Biochemistry
KW - Molecular Biology
KW - Pharmacology
KW - Drug Discovery
SN - 2451-9456
TI - Design on a rational basis of high-affinity peptides inhibiting the histone chaperone ASF1
VL - 26
ER -
TY - JOUR
AB - Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.
AU - Ramananarivo, Sophie
AU - Ducrot, Etienne
AU - Palacci, Jérémie A
ID - 9060
IS - 1
JF - Nature Communications
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Physics and Astronomy
KW - General Chemistry
SN - 2041-1723
TI - Activity-controlled annealing of colloidal monolayers
VL - 10
ER -
TY - JOUR
AB - We investigate the quantum Jensen divergences from the viewpoint of joint convexity. It turns out that the set of the functions which generate jointly convex quantum Jensen divergences on positive matrices coincides with the Matrix Entropy Class which has been introduced by Chen and Tropp quite recently.
AU - Virosztek, Daniel
ID - 405
JF - Linear Algebra and Its Applications
TI - Jointly convex quantum Jensen divergences
VL - 576
ER -
TY - JOUR
AB - We consider real symmetric or complex hermitian random matrices with correlated entries. We prove local laws for the resolvent and universality of the local eigenvalue statistics in the bulk of the spectrum. The correlations have fast decay but are otherwise of general form. The key novelty is the detailed stability analysis of the corresponding matrix valued Dyson equation whose solution is the deterministic limit of the resolvent.
AU - Ajanki, Oskari H
AU - Erdös, László
AU - Krüger, Torben H
ID - 429
IS - 1-2
JF - Probability Theory and Related Fields
SN - 01788051
TI - Stability of the matrix Dyson equation and random matrices with correlations
VL - 173
ER -
TY - JOUR
AB - We count points over a finite field on wild character varieties,of Riemann surfaces for singularities with regular semisimple leading term. The new feature in our counting formulas is the appearance of characters of Yokonuma–Hecke algebras. Our result leads to the conjecture that the mixed Hodge polynomials of these character varieties agree with previously conjectured perverse Hodge polynomials of certain twisted parabolic Higgs moduli spaces, indicating the
possibility of a P = W conjecture for a suitable wild Hitchin system.
AU - Hausel, Tamas
AU - Mereb, Martin
AU - Wong, Michael
ID - 439
IS - 10
JF - Journal of the European Mathematical Society
TI - Arithmetic and representation theory of wild character varieties
VL - 21
ER -
TY - JOUR
AU - Kalinin, Nikita
AU - Shkolnikov, Mikhail
ID - 441
IS - 3
JF - European Journal of Mathematics
SN - 2199-675X
TI - Tropical formulae for summation over a part of SL(2,Z)
VL - 5
ER -
TY - JOUR
AB - A representation formula for solutions of stochastic partial differential equations with Dirichlet boundary conditions is proved. The scope of our setting is wide enough to cover the general situation when the backward characteristics that appear in the usual formulation are not even defined in the Itô sense.
AU - Gerencser, Mate
AU - Gyöngy, István
ID - 301
IS - 3
JF - Stochastic Processes and their Applications
TI - A Feynman–Kac formula for stochastic Dirichlet problems
VL - 129
ER -
TY - JOUR
AB - We study spaces of modelled distributions with singular behaviour near the boundary of a domain that, in the context of the theory of regularity structures, allow one to give robust solution theories for singular stochastic PDEs with boundary conditions. The calculus of modelled distributions established in Hairer (Invent Math 198(2):269–504, 2014. https://doi.org/10.1007/s00222-014-0505-4) is extended to this setting. We formulate and solve fixed point problems in these spaces with a class of kernels that is sufficiently large to cover in particular the Dirichlet and Neumann heat kernels. These results are then used to provide solution theories for the KPZ equation with Dirichlet and Neumann boundary conditions and for the 2D generalised parabolic Anderson model with Dirichlet boundary conditions. In the case of the KPZ equation with Neumann boundary conditions, we show that, depending on the class of mollifiers one considers, a “boundary renormalisation” takes place. In other words, there are situations in which a certain boundary condition is applied to an approximation to the KPZ equation, but the limiting process is the Hopf–Cole solution to the KPZ equation with a different boundary condition.
AU - Gerencser, Mate
AU - Hairer, Martin
ID - 319
IS - 3-4
JF - Probability Theory and Related Fields
SN - 01788051
TI - Singular SPDEs in domains with boundaries
VL - 173
ER -
TY - JOUR
AB - With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.
AU - Igler, Claudia
AU - Abedon, Stephen T.
ID - 6717
JF - Frontiers in Microbiology
TI - Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision
VL - 10
ER -