Genome-wide absolute quantification of chromatin looping.

3D genomics methods such as Hi-C and Micro-C have uncovered chromatin loops across the genome and linked these loops to gene regulation. However, these methods only measure 3D interaction probabilities on a relative scale. Here, we overcome this limitation by using live imaging data to calibrate Micro-C in mouse embryonic stem cells, thus obtaining absolute looping probabilities for 36,804 chromatin loops across the genome.

The searchable chromosome.

To date, genome structure and dynamics have been studied mostly independently; their interplay is a notable blind spot of the field. Brückner, Chen, et al. recently demonstrated an integrated experimental approach sensitive to both, uncovering a striking robustness of enhancer-promoter search times (dynamics) to changes in genomic separation (structure).

Signatures of irreversibility in microscopic models of flocking.

Flocking in d=2 is a genuine nonequilibrium phenomenon for which irreversibility is an essential ingredient. We study a class of minimal flocking models whose only source of irreversibility is self-propulsion and use the entropy production rate (EPR) to quantify the departure from equilibrium across their phase diagrams. The EPR is maximal in the vicinity of the order-disorder transition, where reshuffling of the interaction network is fast.

Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics.

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we introduce an approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observed viscoelastic displacements over micrometers within minutes in response to near-piconewton forces, which are consistent with a Rouse polymer model.

Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging.

Animal genomes are folded into loops and topologically associating domains (TADs) by CTCF and loop-extruding cohesins, but the live dynamics of loop formation and stability remain unknown. Here, we directly visualized chromatin looping at the TAD in mouse embryonic stem cells using super-resolution live-cell imaging and quantified looping dynamics by Bayesian inference. Unexpectedly, the loop was both rare and dynamic, with a looped fraction of approximately 3 to 6.

Electroconvulsive Therapy Hasn't Negative Effects on Short-Term Memory Function, as Assessed Using a Bedside Hand-Held Device.

Electroconvulsive therapy (ECT) is effective in the treatment of treatment-resistant major depression. The fear of cognitive impairment after ECT often deters patients from choosing this treatment option. There is little reliable information regarding the effects of ECT on overall cognitive performance, while short-term memory deficits are well known but not easy to measure within clinical routines.

Surface Trafficking of APP and BACE in Live Cells.

Amyloid-β (Aβ)-peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of Aβ precursor protein (APP) by β-site APP-cleaving enzyme (BACE). Using live-cell imaging of APP and BACE labeled with pH-sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by α-secretase on the cellular surface after exocytosis.

Spot quantification in two dimensional gel electrophoresis image analysis: comparison of different approaches and presentation of a novel compound fitting algorithm.

Background: Various computer-based methods exist for the detection and quantification of protein spots in two dimensional gel electrophoresis images. Area-based methods are commonly used for spot quantification: an area is assigned to each spot and the sum of the pixel intensities in that area, the so-called volume, is used a measure for spot signal. Other methods use the optical density, i.