Breast cancer risk is influenced by rare coding variants in susceptibility genes such as BRCA1 and many common, mainly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. We report results from a genome-wide association study (GWAS) of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry1. We identified 65 new loci associated with overall breast cancer at p<5x10-8. The majority of credible risk SNPs in the new loci fall in distal regulatory elements, and by integrating in-silico data to predict target genes in breast cells at each locus, we demonstrate a strong overlap between candidate target genes and somatic driver genes in breast tumours. We also find that heritability of breast cancer due to all SNPs in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the utility of genetic risk scores for individualized screening and prevention.

Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala × Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r 2 = 24-37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops.Oryza sativa | QTL | three-dimensional | live root imaging | multivariate analysis R oot systems are high-value targets for crop improvement because of their potential to boost or stabilize yields in saline, dry, and acid soils, improve disease resistance, and reduce the need for unsustainable fertilizers (1-7). Root system architecture (RSA) describes the spatial organization of root systems, which is critical for root function in challenging environments (1-10). Modern genomics could allow us to leverage both natural and engineered variation to breed more efficient crops, but the lack of parallel advances in plant phenomics is widely considered to be a primary hindrance to developing "next-generation" agriculture (3,11,12). Root imaging and analysis have been particularly intractable: Decades of phenotyping efforts have failed to identify genes controlling quantitative RSA traits in crop species. Several factors confound RSA gene identification, including polygenic inheritance of root traits, soil opacity, and a complex 3D morphology that can be influenced heavily by the environment. Most phenotyping efforts have relied on small numbers of basic measurements to extrapolate system-wide traits. For example, given the length and mass of a few sample roots and the excavated root system mass, one can estimate the total root length, volume, and average root width of the entire root system (13,14). Other common measurements involve measuring the root surface exposed on a soil core or pressed against a transparent surface to estimate root coverage at a certain soil horizon. In these cases, the choices of sample roots and phenotyping standards, the size and shape of the container, and the limitations of 2D descriptions of 3D struct...

50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially-regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input. Single-molecule imaging shows that this step lowers transcription factor residence time and non-specific collisions during sampling for DNA targets. Third, chromatin interactions shift from long-range to predominantly short-range, and CTCF-mediated loops and contact domains double in numbers. This architectural change facilitates cognate promoter-enhancer contacts and also requires Myc and continual ATP production. Our results thus define the nature and transcriptional impact of chromatin decondensation and reveal an unexpected role for Myc in the establishment of nuclear topology in mammalian cells.

Root system growth and development is highly plastic and is influenced by the surrounding environment. Roots frequently grow in heterogeneous environments that include interactions from neighboring plants and physical impediments in the rhizosphere. To investigate how planting density and physical objects affect root system growth, we grew rice in a transparent gel system in close proximity with another plant or a physical object. Root systems were imaged and reconstructed in three dimensions. Root-root interaction strength was calculated using quantitative metrics that characterize the extent to which the reconstructed root systems overlap each other. Surprisingly, we found the overlap of root systems of the same genotype was significantly higher than that of root systems of different genotypes. Root systems of the same genotype tended to grow toward each other but those of different genotypes appeared to avoid each other. Shoot separation experiments excluded the possibility of aerial interactions, suggesting root communication. Staggered plantings indicated that interactions likely occur at root tips in close proximity. Recognition of obstacles also occurred through root tips, but through physical contact in a size-dependent manner. These results indicate that root systems use two different forms of communication to recognize objects and alter root architecture: root-root recognition, possibly mediated through root exudates, and root-object recognition mediated by physical contact at the root tips. This finding suggests that root tips act as local sensors that integrate rhizosphere information into global root architectural changes.3D reconstruction | imaging | kin recognition P lants interact with the environment in a number of ways (1, 2).Aboveground tissues may identify volatile cues that provide information about their neighbors (3, 4) and detect irradiance, directional light, and light quality (5), whereas belowground tissues, such as roots, can detect changes in soil moisture, nutrient availability, and physical obstacles (6-8). Plants not only detect but also respond to changes in their environment, exhibiting adaptation in their morphology and physiology in response to environmental stimuli (9-14), such as alteration in total root length, root system volume, and root depth (15,16). Phenotypic plasticity of plants in response to environmental heterogeneity may have consequences for plant fitness.Communication among plants is mediated by interactions that take place aboveground (17, 18) and belowground (2,(19)(20)(21). Aboveground interactions have been studied in greater detail, in part because of the accessibility of aerial tissue. However, there is growing interest in root-system architecture and its effect on plant function and fitness (12, 15). Studies of root-system architecture suggest that root systems develop differently in the presence of other root systems. For example, when exposed to the roots of a neighboring plant, common bean plants altered the vertical and horizontal distribution of roo...

Insufficient brightness of fluorophores poses a major bottleneck for the advancement of super-resolution microscopes. Despite being widely used, many rhodamine dyes exhibit sub-optimal brightness due to the formation of twisted intra­molecular charge transfer (TICT) upon photoexcitation. Herein, we have developed a new class of quaternary piperazine-substituted rhodamines with outstanding quantum yields (Φ = 0.93) and superior brightness (ε × Φ = 8.1 × 104 L·mol–1·cm–1), by utilizing the electronic inductive effect to prevent TICT. We have also successfully deployed these rhodamines in the super-resolution imaging of the microtubules of fixed cells and of the cell membrane and lysosomes of live cells. Finally, we demonstrated that this strategy was generalizable to other families of fluorophores, resulting in substantially increased quantum yields.

Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

Rhodamine derivatives and analogues have been widely used for different super-resolution imaging techniques, including photoactivated localization microscopy (PALM). Among them, rhodamine spirolactams exhibit great superiority for PALM imaging due to a desirable bright–dark contrast during the photochromic switching process. Although considerable attention has been paid to the chemical modifications on rhodamine spirolactams, the on-time of photochromic switching, one of the key characteristics for PALM imaging, has never been optimized in previous developments. In this study, we proposed that simply installing a carboxyl group close to the lactam site could impose an intramolecular acidic environment, stabilize the photoactivated zwitterionic structure, and thus effectively increase the on-time. On the basis of this idea, we have synthesized a new rhodamine spirolactam, Rh-Gly, that demonstrated considerably longer on-time than the other tested analogues, as well as an enhancement of single-molecule brightness, an improvement on signal-to-noise ratio and an enlargement of total collected photons of a single molecule before photobleaching. Finally, super-resolution images of live cell mitochondria stained with Rh-Gly have been obtained with a good temporal resolution of 10 s, as well as a satisfactory localization precision of ∼25 nm. Through self-labeling protein tags, Rh-Gly modified with a HaloTag ligand enabled super-resolution imaging of histone H2B proteins in live HeLa cells; through immunostaining antibodies labeled with an isothiocyanate-substituted Rh-Gly, super-resolution imaging of microtubules was achieved in fixed cells. Therefore, our simple and effective strategy provides novel insight for developing further enhanced rhodamine spirolactams recommendable for PALM imaging.

BackgroundGiven their adaptation to nutrient-poor and drought environments, cycads are vital models for plant-microbiome interaction research because they are likely to host an important reservoir of beneficial microbes that may support cycad survival. However, a comprehensive understanding of the diversity and community composition of microbiome associated with different plant compartments as well as bulk soils of cycad species remains elusive.MethodAn extensive investigation of species diversity and community composition of bacterial and fungal microbiome in roots, seeds, unfertilized seeds, ovules, pollens, and soils of Cycas panzhihuaensis L. Zhou & S. Y. Yang has been conducted by high-through sequencing technology. Moreover, principal component analysis (PCA), hierarchical cluster analysis (HCA), and heatmap analysis were applied to test the niche-specific effect and biogeography factor among different sample types of this cycad species.ResultsHighly diverse microbiota and significant variation of community structure were found among different compartments of C. panzhihuaensis. Soils exhibited a remarkable differentiation of bacterial community composition compared to the other five plant organs as revealed by PCA, HCA, and heatmap analyses. Different compartments possessed unique core microbial taxa with Pseudomonadaceae and Nectriaceae shared among them. According to the indicator species analysis, there was almost no differentiation of dominant microbiomes with regard to the geography of the host cycad. Two main transmission models existed in the C. panzhihuaensis.ConclusionsEach sample type represented a unique niche and hosted a niche-specific core microbial taxa. Contrary to previous surveys, biogeography hardly exerted impact on microbial community variation in this study. The majority of the cycad-associated microbes were horizontally derived from soils and/or air environments with the rest vertically inherited from maternal plants via seeds. This study offers a robust knowledge of plant-microbiome interaction across various plant compartments and soils and lends guidelines to the investigation of adaptation mechanism of cycads in arid and nutrient-poor environments as well as their evolutionary conservation.