BAZ2A safeguards genome architecture of ground‐state pluripotent stem cells

Chromosomes have an intrinsic tendency to segregate into compartments, forming long‐distance contacts between loci of similar chromatin states. How genome compartmentalization is regulated remains elusive. Here, comparison of mouse ground‐state embryonic stem cells (ESCs) characterized by open and active chromatin, and advanced serum ESCs with a more closed and repressed genome, reveals distinct regulation of their genome organization due to differential dependency on BAZ2A/TIP5, a component of the chromatin remodeling complex NoRC. On ESC chromatin, BAZ2A interacts with SNF2H, DNA topoisomerase 2A (TOP2A) and cohesin. BAZ2A associates with chromatin sub‐domains within the active A compartment, which intersect through long‐range contacts. We found that ground‐state chromatin selectively requires BAZ2A to limit the invasion of active domains into repressive compartments. BAZ2A depletion increases chromatin accessibility at B compartments. Furthermore, BAZ2A regulates H3K27me3 genome occupancy in a TOP2A‐dependent manner. Finally, ground‐state ESCs require BAZ2A for growth, differentiation, and correct expression of developmental genes. Our results uncover the propensity of open chromatin domains to invade repressive domains, which is counteracted by chromatin remodeling to establish genome partitioning and preserve cell identity.     

Scaling of Surface Plasmon Resonances in Triangular Silver Nanoplate Sols for Enhanced Refractive Index Sensing

The plasmonic spectra of solution phase ensembles of triangular silver nanoplates have been analysed in order to examine the fundamental properties underlying their size-dependent enhanced refractive index sensitivities. Linewidth studies highlight variations in the response of these solution phase nanostructures to those previously reported for single immobilized triangular nanostructures. The observation of insignificant broadening of the resonance linewidth for larger edge length nanoplates highlights minimal contribution of radiative damping processes at these dimensions. Comparative single nanoplate studies using discrete dipole approximations were performed to analyse the dephasing processes contributing to these reduced linewidths and to determine the key parameters defining the underlying plasmonic response. These single nanoplate approximations highlight the dominance of absorption processes over radiative processes and demonstrate that this dominance can be attributed to the platelet nature/geometry of the nanoplates. These calculations indicate that the higher aspect ratio allows for the maintenance of coherent plasmon oscillations as the edge length of the triangular platelet increases within the sols. Thickness studies verify that this reduction in radiation damping is due to high aspect ratio and can act to confine electromagnetic fields at the nanoplate surface, thereby increasing near-field enhancement and hence the resultant plasmonic refractive index sensitivity.     

Evolutionary novelty in communication between the sexes

The diversity of signalling traits within and across taxa is vast and striking, prompting us to consider how novelty evolves in the context of animal communication. Sexual selection contributes to diversification, and here we endeavour to understand the initial conditions that facilitate the maintenance or elimination of new sexual signals and receiver features. New sender and receiver variants can occur through mutation, plasticity, hybridization and cultural innovation, and the initial conditions of the sender, the receiver and the environment then dictate whether a novel cue becomes a signal. New features may arise in the sender, the receiver or both simultaneously. We contend that it may be easier than assumed to evolve new sexual signals because sexual signals may be arbitrary, sexual conflict is common and receivers are capable of perceiving much more of the world than just existing sexual signals. Additionally, changes in the signalling environment can approximate both signal and receiver changes through a change in transmission characteristics of a given environment or the use of new environments. The Anthropocene has led to wide-scale disruption of the environment and may thus generate opportunity to directly observe the evolution of new signals to address questions that are beyond the reach of phylogenetic approaches.     

Precise Estimates of Persistence Time for SIS Infections in Heterogeneous Populations

For a susceptible–infectious–susceptible infection model in a heterogeneous population, we derive simple and precise estimates of mean persistence time, from a quasi-stationary endemic state to extinction of infection. Heterogeneity may be in either individuals’ levels of infectiousness or of susceptibility, as well as in individuals’ infectious period distributions. Infectious periods are allowed to follow arbitrary non-negative distributions. We also obtain a new and accurate approximation to the quasi-stationary distribution of the process, as well as demonstrating the use of our estimates to investigate the effects of different forms of heterogeneity. Our model may alternatively be interpreted as describing an infection spreading through a heterogeneous directed network, under the annealed network approximation.     

Nature and prevalence of combinations of mental disorders and their association with excess mortality in a population‐based cohort study

The nature and prevalence of combinations of mental disorders and their associations with premature mortality have never been reported in a comprehensive way. We describe the most common combinations of mental disorders and estimate excess mortality associated with these combinations. We designed a population‐based cohort study including all 7,505,576 persons living in Denmark at some point between January 1, 1995 and December 31, 2016. Information on mental disorders and mortality was obtained from national registers. A total of 546,090 individuals (10.5%) living in Denmark on January 1, 1995 were diagnosed with at least one mental disorder during the 22‐year follow‐up period. The overall crude rate of diagnosis of mental disorders was 9.28 (95% CI: 9.26‐9.30) per 1,000 person‐years. The rate of diagnosis of additional mental disorders was 70.01 (95% CI: 69.80‐70.26) per 1,000 person‐years for individuals with one disorder already diagnosed. At the end of follow‐up, two out of five individuals with mental disorders were diagnosed with two or more disorder types. The most prevalent were neurotic/stress‐related/somatoform disorders (ICD‐10 F40‐F48) and mood disorders (ICD‐10 F30‐F39), which – alone or in combination with other disorders – were present in 64.8% of individuals diagnosed with any mental disorder. Mortality rates were higher for people with mental disorders compared to those without mental disorders. The highest mortality rate ratio was 5.97 (95% CI: 5.52‐6.45) for the combination of schizophrenia (ICD‐10 F20‐F29), neurotic/stress‐related/somatoform disorders and substance use disorders (ICD‐10 F10‐F19). Any combination of mental disorders was associated with a shorter life expectancy compared to the general Danish population, with differences in remaining life expectancy ranging from 5.06 years (95% CI: 5.01‐5.11) to 17.46 years (95% CI: 16.86‐18.03). The largest excess mortality was observed for combinations that included substance use disorders. This study reports novel estimates related to the “force of comorbidity” and provides new insights into the contribution of substance use disorders to premature mortality in those with comorbid mental disorders.