The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Allostatic load and incident heart failure in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study

Abstract Background Allostatic load (AL) is the physiologic “wear and tear” on the body from stress. Yet, despite stress being implicated in the development heart failure (HF), it is unknown whether AL is associated with incident HF events. Methods We examined 16,765 participants without HF at baseline from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The main exposure was AL score quartile. AL was determined according to 11 physiologic parameters, whereby each parameter was assigned points (0–3) based on quartiles within the sample, and points were summed to create a total AL score ranging from 0–33. The outcome was incident HF event. We examined the association between AL quartile (Q1-Q4) and incident HF events using Cox proportional hazards models, adjusted for demographics, socioeconomic factors, and lifestyle. Results The mean age was 64 ± 9.6 years, 61.5% were women, and 38.7% were Black participants. Over a median follow up of 11.4 years, we observed 750 incident HF events (635 HF hospitalizations and 115 HF deaths). Compared to the lowest AL quartile (Q1), the fully adjusted hazards of an incident HF event increased in a graded fashion: Q2 HR 1.49 95% CI 1.12–1.98; Q3 HR 2.47 95% CI 1.89–3.23; Q4 HR 4.28 95% CI 3.28–5.59. The HRs for incident HF event in the fully adjusted model that also adjusted for CAD were attenuated, but remained significant and increased in a similar, graded fashion by AL quartile. There was a significant age interaction (p-for-interaction < 0.001), whereby the associations were observed across each age stratum, but the HRs were highest among those aged < 65 years. Conclusion AL was associated with incident HF events, suggesting that AL could be an important risk factor and potential target for future interventions to prevent HF

Isolation and Genome Sequencing of Two Novel Mycobacteriophages, Optimus and Sassafras

Twenty new mycobacteriophages, capable of infecting Mycobacterium smegmatis, were isolated from soil samples collected on or nearby Hope College in Holland, Michigan. Collectively, the group displayed a variety of plaque morphologies indicating an assortment of different phages. Both lytic and temperate phages appear represented in this collection. Purified phage stocks were used to prepare genomic DNA samples for restriction digest analysis. Of 20 samples analyzed, a total of 13 phages produced just 4 types of restriction digest patterns indicating some degree of relatedness among some of our new phage isolates. Interestingly, one group of 4 phages (Optimus, Lynx, Aurora and TheCube14) that yielded a similar restriction digest pattern, were all isolated from mulch-covered soil at a depth of 4-8 cm. Two phages (Optimus and Sassafras) were chosen for complete genome sequencing and comparative genomic analyses. Both phages produced plaques of between 1-2 mm in diameter at 24 hours that enlarged to about 4 mm in diameter after 48 hours of incubation at 37°C. Whereas continued incubation of phage Optimus resulted in cessation of plaque growth by 72 hours, plaques produced by Sassafras continued to enlarge beyond 8 days, reaching a diameter of greater than 10 mm. Phage Optimus produced plaques that displayed a clear center surrounded by turbid rings. Phage Sassafras produced clear plaques with defined edges at 24 hours, but all subsequent growth was progressively more turbid in nature, resulting in plaques with a turbid ring around a center clear zone. Comparison of the restriction digest patterns for Optimus and Sassafras with more than 60 existing mycobacteriophage genomes indicates that Optimus may be a new representative of cluster H, while Sassafras shows some similarity to the F cluster of mycobacteriophages. Results of our analyses of both genomes are reported

Single-cell, whole-embryo phenotyping of mammalian developmental disorders.

Mouse models are a critical tool for studying human diseases, particularly developmental disorders1. However, conventional approaches for phenotyping may fail to detect subtle defects throughout the developing mouse2. Here we set out to establish single-cell RNA sequencing of the whole embryo as a scalable platform for the systematic phenotyping of mouse genetic models. We applied combinatorial indexing-based single-cell RNA sequencing3 to profile 101 embryos of 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than 1.6 million nuclei. The 22 mutants represent a range of anticipated phenotypic&nbsp;severities, from established multisystem disorders to deletions of individual regulatory regions4,5. We developed and applied several analytical frameworks for detecting differences in composition and/or gene expression across 52 cell types or trajectories. Some mutants exhibit changes in dozens of trajectories whereas others exhibit changes in only a few cell types. We also identify differences between widely used wild-type strains, compare phenotyping of gain- versus loss-of-function mutants and characterize deletions of topological associating domain boundaries. Notably, some changes are shared among mutants, suggesting that developmental pleiotropy might be decomposable through further scaling of this approach. Overall, our findings show how single-cell profiling of whole embryos can enable the systematic molecular and cellular phenotypic characterization of mouse mutants with unprecedented breadth and resolution

SCF\u3b2-TRCP suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2.

SCF\u3b2-TRCP suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2