Optical Measurement of Mechanical Forces Inside Short DNA Loops

ABSTRACT Knowledge of the mechanical properties of double-stranded DNA (dsDNA) is essential to understand the role of dsDNA looping in gene regulation and the mechanochemistry of molecular machines that operate on dsDNA. Here, we use a newly developed tool, force sensors with optical readout, to measure the forces inside short, strained loops composed of both dsDNA and single-stranded DNA. By varying the length of the loops and their proportion of dsDNA, it was possible to vary their internal forces from 1 pN to .20 pN. Surprisingly, internal loop forces changed erratically as the amount of dsDNA was increased for a given loop length, with the effect most notable in the smallest loop (57 nucleotides). Monte Carlo simulations based on the helical wormlike chain model accurately predict internal forces when more than half of the loop is dsDNA but fail otherwise. Mismatches engineered into the double-stranded regions increased flexibility, suggesting that Watson-Crick basepaired dsDNA can withstand high compressive forces without recourse to multibase melts. Fluorescence correlation spectroscopy further excluded transient melting (microsecond to millisecond duration) as a mechanism for relief of compressive forces in the tested dsDNAs. DNA loops with integrated force sensors may allow the comprehensive mapping of the elasticity of short dsDNAs as a function of both sequence and salt

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Seafarer citizen scientist ocean transparency data as a resource for phytoplankton and climate research

The oceans' phytoplankton that underpin the marine food chain appear to be changing in abundance due to global climate change. Here, we compare the first four years of data from a citizen science ocean transparency study, conducted by seafarers using home-made Secchi Disks and a free Smartphone application called Secchi, with contemporaneous satellite ocean colour measurements. Our results show seafarers collect useful Secchi Disk measurements of ocean transparency that could help future assessments of climate-induced changes in the phytoplankton when used to extend historical Secchi Disk data

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

Highly parallel genome variant engineering with CRISPR-Cas9.

Understanding the functional effects of DNA sequence variants is of critical importance for studies of basic biology, evolution, and medical genetics; however, measuring these effects in a high-throughput manner is a major challenge. One promising avenue is precise editing with the CRISPR-Cas9 system, which allows for generation of DNA double-strand breaks (DSBs) at genomic sites matching the targeting sequence of a guide RNA (gRNA). Recent studies have used CRISPR libraries to generate many frameshift mutations genome wide through faulty repair of CRISPR-directed breaks by nonhomologous end joining (NHEJ) 1 . Here, we developed a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. We used our method to examine the functional consequences of premature-termination codons (PTCs) at different locations within all annotated essential genes in yeast. We found that most PTCs were highly deleterious unless they occurred close to the 3' end of the gene and did not affect an annotated protein domain. Unexpectedly, we discovered that some putatively essential genes are dispensable, whereas others have large dispensable regions. This approach can be used to profile the effects of large classes of variants in a high-throughput manner