The spatial segregation of pericentromeric heterochromatin (PCH) into distinct, membrane-less nuclear compartments involves the binding of Heterochromatin Protein 1 (HP1) to H3K9me2/3-rich genomic regions. While HP1 exhibits liquid-liquid phase separation properties in vitro, its mechanistic impact on the structure and dynamics of PCH condensate formation in vivo remains largely unresolved. Here, using a minimal theoretical framework, we systematically investigate the mutual coupling between self-interacting HP1-like molecules and the chromatin polymer. We reveal that the specific affinity of HP1 for H3K9me2/3 loci facilitates coacervation in nucleo and promotes the formation of stable PCH condensates at HP1 levels far below the concentration required to observe phase separation in purified protein assays in vitro. These heterotypic HP1-chromatin interactions give rise to a strong dependence of the nucleoplasmic HP1 density on HP1-H3K9me2/3 stoichiometry, consistent with the thermodynamics of multicomponent phase separation. The dynamical cross talk between HP1 and the viscoelastic chromatin scaffold also leads to anomalously slow equilibration kinetics, which strongly depend on the genomic distribution of H3K9me2/3 domains and result in the coexistence of multiple long-lived, microphase-separated PCH compartments. The morphology of these complex coacervates is further found to be governed by the dynamic establishment of the underlying H3K9me2/3 landscape, which may drive their increasingly abnormal, aspherical shapes during cell development. These findings compare favorably to 4D microscopy measurements of HP1 condensate formation in live Drosophila embryos and suggest a general quantitative model of PCH formation based on the interplay between HP1-based phase separation and chromatin polymer mechanics.

Purpose

Recent doubts regarding the efficacy may have resulted in a loss of interest for targeted temperature management (TTM) in comatose cardiac arrest (CA) patients, with uncertain consequences on outcome. We aimed to identify a change in TTM use and to assess the relationship between this change and neurological outcome.

Methods

We used Utstein data prospectively collected in the Sudden Death Expertise Center (SDEC) registry (capturing CA data from all secondary and tertiary hospitals located in the Great Paris area, France) between May 2011 and December 2017. All cases of non-traumatic OHCA patients with stable return of spontaneous circulation (ROSC) were included. After adjustment for potential confounders, we assessed the relationship between changes over time in the use of TTM and neurological recovery at discharge using the Cerebral Performance Categories (CPC) scale.

Results

Between May 2011 and December 2017, 3925 patients were retained in the analysis, of whom 1847 (47%) received TTM. The rate of good neurological outcome at discharge (CPC 1 or 2) was higher in TTM patients as compared with no TTM (33% vs 15%, P < 0.001). Gender, age, and location of CA did not change over the years. Bystander CPR increased from 55% in 2011 to 73% in 2017 (P < 0.001) and patients with a no-flow time longer than 3 min decreased from 53 to 38% (P < 0.001). The use of TTM decreased from 55% in 2011 to 37% in 2017 (P < 0.001). Meanwhile, the rate of patients with good neurological recovery remained stable (19 to 23%, P = 0.76). After adjustment, year of CA occurrence was not associated with outcome.

Conclusions

We report a progressive decrease in the use of TTM in post-cardiac arrest patients over the recent years. During this period, neurological outcome remained stable, despite an increase in bystander-initiated resuscitation and a decrease in "no flow" duration.

A defining signature of strongly correlated electronic systems is a rich phase diagram, which consists of multiple broken symmetries, such as magnetism, superconductivity and charge order1,2. In the recently discovered nickelate superconductors3–10, a large antiferromagnetic exchange energy has been reported, which implies the existence of strong electronic correlations11. However, signatures of a broken-symmetry state other than superconductivity have not yet been observed. Here we observe charge ordering in infinite-layer nickelates La1−xSrxNiO2 using resonant X-ray scattering. The parent compound orders along the Ni–O bond direction with an incommensurate wavevector, distinct from the stripe order observed in other nickelates12–14 that propagates along a direction 45° to the Ni–O bond. The resonance profile we measure indicates that ordering originates from the nickelate layers and induces a parasitic charge modulation of lanthanum electrons. Upon doping, the charge order diminishes and its wavevector shifts towards commensurate, hinting that strong electronic correlations are likely to be responsible for the ordered state. Our results suggest that the existence of charge order and its potential interplay with antiferromagnetic fluctuations and superconductivity are important themes in nickel-based superconductors.