Double-strand breaks (DSBs) threaten genomic stability and need immediate attention from DNA damage response (DDR) machinery involved in homologous recombination (HR) or nonhomologous end joining (NHEJ). DDR in heterochromatin is challenging owing to the distinct chromatin organization. Heterochromatin protein 1 (HP1) isoforms are central to heterochromatin structure and have been implicated in DDR. Mammalian HP1 has three isoforms, HP1α, HP1β, and HP1γ, which possess significant homology and yet have distinct functions. HP1α is the only isoform known to undergo liquid-liquid phase separation mediated by phosphorylation on the N-terminal extension (NTE). We show that the minute-scale dynamics of HP1α and HP1β differ dramatically and differentially influence the recruitment of HR vs. NHEJ factors at sites of laser-induced clustered DSBs. Perturbing HP1α phosphorylation impairs HR factor recruitment and reduces HR efficiency. Our study provides a potential link between phase separation and DDR-centric roles of HP1α and hints at spatial partitioning of repair pathways in response to damage in heterochromatin.

Molecules that violate Hund's rule by exhibiting an inverted singlet-triplet gap (STG), where the first excited singlet ( ) lies below the triplet ( ), are rare but hold great promise as efficient fifth-generation light emitters. Azaphenalenes (APs) represent one of the few known molecular classes capable of such inversion of the / energy ordering, yet a systematic exploration of all unique APs is lacking. Here, we investigate 104 distinct APs and classify them based on their adherence to or deviation from Hund's rule using - gaps computed with the second-order coupled-cluster method employing the Laplace transform (L-CC2). To capture substitution-dependent pseudo-Jahn-Teller distortions that are inadequately described by MP2 and DFT methods, we employ a focal-point extrapolation scheme to obtain near-CCSD(T)/cc-pVTZ-quality geometries. We find 3 APs to undergo and 10 to show symmetry lowering, leading to a total of 117 configurations of 104 unique APs. Our study identifies top candidates with inverted STGs, revealing how substitution and symmetry-lowering modulate these gaps to uncover new stable AP cores that provide promising targets for designing molecular light-emitters.

Adopted in December 2022, the Kunming-Montreal Global Biodiversity Framework (KMGBF) under the Convention on Biological Diversity outlines a visionary road map guiding humanity's relationship with nature. KMGBF commitments require active intervention, sustained monitoring and scientific reporting, capacity building for tools and technologies, and cooperation among 196 signatories. Genetic diversity, which underlies adaptation and fitness, is a core tenet of the KMGBF. This article aims to distill the KMGBF to help researchers, practitioners, and other interested parties achieve its commitments. In five sections, we address (a) the KMGBF's terminology and scope, (b) the intersection of KMGBF targets with genetic diversity, (c) genetic monitoring for tracking its progress, (d) paradigms and decision frameworks to guide genetic conservation actions, and (e) emerging frontiers. A better understanding of the KMGBF will help researchers, practitioners, and other interested parties more effectively engage and fulfill global, national, and local commitments to the conservation of our planet's biodiversity.

We present the first detailed multi-tracer observation of a 5-pc long outer Galaxy filament, G183, and the massive young stellar object (YSO) IRAS 05480+2545 associated with it. Using the IRAM 30-m telescope at lambda = 1.4 and 3 mm, we probed the molecular gas distribution at angular resolutions of ~12"-28" (0.1-0.3 pc at d = 2.1 kpc). The velocity-resolved C18O(1-0) observations conclusively show a main filament with a skeleton of ridges. The main filament is a 5 pc long velocity-coherent structure with a continuous and quiescent velocity field along its length up to the star-forming hub that accretes mass from the filament. The internal gas kinematics of most of the G183 filament is dominated by thermal motions (sigma_NT/cs~1) and large-scale velocity gradients arising due to outflows and accretion of matter in the massive YSO. The dispersion-size relation almost up to 1 pc is consistent with Larson's law, suggesting that the origin of the filament is a turbulence cascade. The massive YSO, S1, with no corresponding radio continuum detection is characterized as a high-mass protostellar object with a mass of 156 Msun and an M/L ratio of 0.04. We identify a kinematic signature of the accretion of material from the filament onto the YSO, S1. The rates of molecular gas accretion and entrainment in S1 are estimated to be 8.6 and 2.6 (in units of 10^-4 Msun/yr), respectively. In comparison to the inner Galaxy high-mass star-forming filaments forming massive stars, G183 has a lower column density; however, the accretion and outflow rates in S1 are similar. The detection of hydrocarbons such as CH3CN and HC3N indicates the presence of hot-core chemistry in S1. These results highlight the universality of physical processes involved in massive star formation across a range of Galactic environments.

Ubiquitination, a post-translational modification, regulates numerous cellular processes by attaching ubiquitin molecules to the target proteins, thereby altering their cellular levels and functions. A central aspect of ubiquitin-mediated signaling is the formation of different types of polyubiquitin (polyUb) chains, which can be either homotypic or heterotypic, generating a variety of cellular signals that activate distinct downstream pathways. Homotypic chains are linked via the same lysine on each molecule, whereas heterotypic chains are conjugated via multiple lysines. The synthesis of these diverse polyubiquitin chains is driven by interactions between substrate-conjugated ubiquitin molecules, ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). However, the molecular details of these interactions and how they govern the synthesis of different homotypic and heterotypic chains remain poorly understood. The E2 enzyme E2-25K preferentially extends K48-linked polyubiquitin chains on K63-linked template polyubiquitin chains, creating branched K48/K63 chains. In this study, we investigated the role of dynamic interactions between E2-25K and the K63-linked diubiquitin substrate to assess the molecular mechanism of branched-chain assembly. Our data reveal that E2-25K shows no preference for binding to the proximal or distal ubiquitin of a template chain. However, binding to the distal unit activates the complex; binding to the proximal unit does not. This study highlights the critical role of stereospecificity in enzyme/substrate interactions for branched ubiquitin chain synthesis and provides insights into the mechanisms of ubiquitin signaling.