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SummaryCell fate acquisition is a fundamental developmental process in all multicellular organisms. Yet, much is unknown regarding how a cell traverses the pathway from stem cell to terminal differentiation. Advances in single cell genomics1 hold promise for unraveling developmental mechanisms2–3 in tissues4, organs5–6, and organisms7–8. However, lineage tracing can be challenging for some tissues9 and integration of high-quality datasets is often necessary to detect rare cell populations and developmental states10,11. Here, we harmonized single cell mRNA sequencing data from over 110,000 cells to construct a comprehensive atlas for a stereotypically developing organ with indeterminate growth, the Arabidopsis root. To test the utility of the atlas to interpret new datasets, we profiled mutants for two key transcriptional regulators at single cell resolution, shortroot and scarecrow. Although both transcription factors are required for early specification of cell identity12, our results suggest the existence of an alternative pathway acting in mature cells to specify endodermal identity, for which SHORTROOT is required. Uncovering the architecture of this pathway will provide insight into specification and stabilization of the endodermis, a tissue analogous to the mammalian epithelium. Thus, the atlas is a pivotal advance for unraveling the transcriptional programs that specify and maintain cell identity to regulate organ development in space and time.

Summary With more sequenced genomes, our understanding of the demographic history of Arabidopsis thaliana is rapidly expanding. However, no‐one has yet compiled previous data to investigate patterns of genetic variation across Eurasia. While sub‐Saharan accessions have been reported to be the most divergent group, in the nuclear genome we found accessions from Yunnan, China to be genetically closest to the sub‐Saharan group. In chloroplast, several deeply diverged haplogroups exist only in Eurasia, and African populations have lower variation in many haplogroups that they share with the Eurasian populations. These patterns cannot be easily explained by a single out‐of‐Africa event suggested previously. For more recent demographic history, we dated the nonrelict expansion to 10 ka. In the Chinese Yangtze nonrelicts, we found clear traces of gene flow with local relicts, and genes under strong selection were enriched for traces of relict introgression, especially those related to biotic and immune responses. The results suggest the ability of nonrelicts to obtain locally adaptive alleles through admixture with relicts is important for the expansion across environmental gradients of Eurasia. Our re‐analyses provide another model for the early history as well as elucidating factors contributing to the recent demographic turnover event of this species.

in Wiley Online Library (wileyonlinelibrary.com).Although many researchers have optimized the operation of seeded batch crystallization, there remains little understanding of the effect of the choice of objective function on the optimization and no consensus on which objective function is best. In this work, different objective functions for seeded batch crystallization are compared by calculating the supersaturation trajectory that minimizes each objective function and then comparing the results of each trajectory. We show that some objective functions lead to trajectories that cause excessive nucleated mass and should be avoided. We conclude that the best objective function in most cases is to minimize the nucleated mass. This also corresponds to maximizing the growth of seeds, and leads to a product with a large volume mean size. We also show that the width of the product crystal size distribution can be controlled much more effectively by manipulating seed properties than by adjusting the supersaturation trajectory.

Balancing selection is frequently invoked as a mechanism that maintains variation within and across populations. However, there are few examples of balancing selection operating on loci underpinning complex traits, which frequently display high levels of variation. We investigated mechanisms that may maintain variation in a focal polymorphism—leaf chemical profiles of a perennial wildflower ( Boechera stricta , Brassicaceae)—explicitly interrogating multiple ecological and genetic processes including spatial variation in selection, antagonistic pleiotropy, and frequency-dependent selection. A suite of common garden and greenhouse experiments showed that the alleles underlying variation in chemical profile have contrasting fitness effects across environments, implicating two ecological drivers of selection on chemical profile: herbivory and drought. Phenotype-environment associations and molecular genetic analyses revealed additional evidence of past selection by these drivers. Together, these data are consistent with balancing selection on chemical profile, likely caused by pleiotropic effects of secondary chemical biosynthesis genes on herbivore defense and drought response.

Brassinosteroids are plant steroid hormones that regulate diverse processes, such as cell division and cell elongation, through gene regulatory networks that vary in space and time. By using time series single-cell RNA sequencing to profile brassinosteroid-responsive gene expression specific to different cell types and developmental stages of the Arabidopsis root, we identified the elongating cortex as a site where brassinosteroids trigger a shift from proliferation to elongation associated with increased expression of cell wall–related genes. Our analysis revealed HOMEOBOX FROM ARABIDOPSIS THALIANA 7 ( HAT7 ) and GT-2-LIKE 1 ( GTL1 ) as brassinosteroid-responsive transcription factors that regulate cortex cell elongation. These results establish the cortex as a site of brassinosteroid-mediated growth and unveil a brassinosteroid signaling network regulating the transition from proliferation to elongation, which illuminates aspects of spatiotemporal hormone responses.

Objectives We investigated whether changes in mammographic technique and screening policy have improved mammographic sensitivity, and elongated the mean sojourn time, since the introduction of biennial breast cancer screening in Nijmegen, the Netherlands, in 1975. Methods Maximum likelihood estimation, non-linear regression, and Markov Chain Monte Carlo simulation were used to estimate test sensitivity, mean sojourn time, and underlying breast cancer incidence in four time periods, covering 40 years of breast cancer screening in Nijmegen (1975–2012). Results Maximum likelihood estimation generated an estimated test sensitivity of approximately 90% and a mean sojourn time around three years, while the estimates based on non-linear regression and Markov Chain Monte Carlo simulation were 80% and four years, respectively. All three methods estimated a rise in the underlying breast cancer incidence over time, with approximately one case more per 1000 women per year in the final period compared with the first period. Conclusions The three methods showed a slightly higher mammographic sensitivity and a longer mean sojourn time in the last period, after the introduction of digital mammography. Estimates were more realistic for the more sophisticated methods, non-linear regression and Markov Chain Monte Carlo simulation, while the simple closed form approximation of maximum likelihood estimation led to rather high estimates for sensitivity in the early periods.

This study investigated the correlation between irritable bowel syndrome (IBS) and organic erectile dysfunction (OED) and psychogenic erectile dysfunction (PED), and analyzed the influence of various comorbidities. Data were obtained from reimbursement claims of the National Health Insurance Program in Taiwan. We selected male patients aged >20 years, who were diagnosed with IBS during the 2000-2011 period as the IBS cohort. The index date for patients with IBS was the date of their first medical visit. We excluded patients with a diagnosis of OED and PED at baseline and those without information on age and sex. The IBS to non-IBS cohorts were estimated using univariable and multivariable Cox proportional hazards regression model. Adjusted hazard ratios were determined after adjusting for age and comorbidities. The Kaplan-Meier method was used to plot the cumulative incidence of OED and PED, and a log-rank test was used to compare the cohorts. A total of 15,533 IBS patients and 62,124 controls without IBS were enrolled in our study. Among the study participants, 48.2% were 49 years of age or younger. Patients with IBS were more likely to develop erectile dysfunction (ED) than those without IBS. Patients with IBS were 2.12 times more likely to develop OED and 2.38 times more likely to develop PED than the controls. There is an increased risk of both PED and OED in patients with IBS. Not only with organic but also PED should be considered when patients with IBS complain of ED.