Cohesin cleavage by separase is enhanced by a substrate motif distinct from the cleavage site.

Chromosome segregation begins when the cysteine protease, separase, cleaves the Scc1 subunit of cohesin at the metaphase-to-anaphase transition. Separase is inhibited prior to metaphase by the tightly bound securin protein, which contains a pseudosubstrate motif that blocks the separase active site. To investigate separase substrate specificity and regulation, here we develop a system for producing recombinant, securin-free human separase. Using this enzyme, we identify an LPE motif on the Scc1 substrate that is distinct from the cleavage site and is required for rapid and specific substrate cleavage. Securin also contains a conserved LPE motif, and we provide evidence that this sequence blocks separase engagement of the Scc1 LPE motif. Our results suggest that rapid cohesin cleavage by separase requires a substrate docking interaction outside the active site. This interaction is blocked by securin, providing a second mechanism by which securin inhibits cohesin cleavage

Mechanisms of ubiquitin transfer by the anaphase-promoting complex

The anaphase-promoting complex (APC) is a ubiquitin-protein ligase required for the completion of mitosis in all eukaryotes. Recent mechanistic studies reveal how this remarkable enzyme combines specificity in substrate binding with flexibility in ubiquitin transfer, thereby allowing the modification of multiple lysines on the substrate as well as specific lysines on ubiquitin itself

Multi-wavelength imaging and spectral analysis of jet-like phenomena in a solar active region using IRIS and AIA

High-resolution observations of dynamic phenomena give insights into the properties and processes that govern the low solar atmosphere. We present an analysis of jet-like phenomena emanating from a penumbral footpoint in active region (AR) 12192 using imaging and spectral observations from the Interface Region Imaging Spectrograph (IRIS) and the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory. These jets are associated with line-of-sight Doppler speeds of ±10–22 km s−1 and bright fronts that seem to move across the plane-of-sky at speeds of 23–130 km s−1. Such speeds are considerably higher than the expected sound speed in the chromosphere. The jets have signatures that are visible both in the cool and hot channels of IRIS and AIA. Each jet lasts on average 15 minutes and occurs 5–7 times over a period of 2 hr. Possible mechanisms to explain this phenomenon are suggested, the most likely of which involve p-mode or Alfvén wave shock trains impinging on the transition region and corona as a result of steepening photospheric wavefronts or gravity waves

Reflection on modern methods: Calculating a sample size for a repeatability sub-study to correct for measurement error in a single continuous exposure

Using a continuous exposure variable that is measured with random error in a univariable linear regression model leads to regression dilution bias: the observed association between the exposure and outcome is smaller than it would be if the true value of the exposure could be used. A repeatability sub-study, where a sample of study participants have their data measured again, can be used to correct for this bias. It is important to perform a sample size calculation for such a sub-study, to ensure that correction factors can be estimated with sufficient precision. We describe how a previously published method can be used to calculate the sample size from the anticipated size of the correction factor and its desired precision, and demonstrate this approach using the example of the cross-sectional studies conducted as part of the International Project on Cardiovascular Disease in Russia study. We also provide correction factors calculated from repeat data from the UK Biobank study, which can be used to help plan future repeatability studies

Inferring the time-dependent complex Ginzburg-Landau equation from modulus data

We present a formalism for inferring the equation of evolution of a complex wave field that is known to obey an otherwise unspecified (2+1)-dimensional time-dependent complex Ginzburg-Landau equation, given field moduli over three closely-spaced planes. The phase of the complex wave field is retrieved via a non-interferometric method, and all terms in the equation of evolution are determined using only the magnitude of the complex wave field. The formalism is tested using simulated data for a generalized nonlinear system with a single-component complex wave field. The method can be generalized to multi-component complex fields.Comment: 9 pages, 9 figure