Accurate thermodynamic parameters improve RNA structure predictions and thus accelerate understanding of RNA function and the identification of RNA drug binding sites. Many viral RNA structures, such as internal ribosome entry sites, have internal loops and bulges that are potential drug target sites. Current models used to predict internal loops are biased toward small, symmetric purine loops, and thus poorly predict asymmetric, pyrimidine-rich loops with >6 nucleotides (nt) that occur frequently in viral RNA. This article presents new thermodynamic data for 40 pyrimidine loops, many of which can form UU or protonated CC base pairs. Uracil and protonated cytosine base pairs stabilize asymmetric internal loops. Accurate prediction rules are presented that account for all thermodynamic measurements of RNA asymmetric internal loops. New loop initiation terms for loops with >6 nt are presented that do not follow previous assumptions that increasing asymmetry destabilizes loops. Since the last 2004 update, 126 new loops with asymmetry or sizes greater than 2 × 2 have been measured. These new measurements significantly deepen and diversify the thermodynamic database for RNA. These results will help better predict internal loops that are larger, pyrimidine-rich, and occur within viral structures such as internal ribosome entry sites.
more »
« less
Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging
Super-resolution live-cell imaging of CTCF- and cohesin-mediated chromatin loops reveals that these loops are rare and dynamic.
more »
« less
- Award ID(s):
- 2036037
- PAR ID:
- 10379463
- Date Published:
- Journal Name:
- Science
- Volume:
- 376
- Issue:
- 6592
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- 496 to 501
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
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. We find that the looped state is generally rare, with a mean probability of 2.3% and a maximum of 26% across the quantified loops. On average, CTCF-CTCF loops are stronger than loops between cis-regulatory elements (3.2% vs. 1.1%). Our findings can be extended to human stem cells and differentiated cells under certain assumptions. Overall, we establish an approach for genome-wide absolute loop quantification and report that loops generally occur with low probabilities, generalizing recent live imaging results to the whole genome.more » « less
-
Unveiling the Dynamics and Genesis of Small-scale Fine-structure Loops in the Lower Solar AtmosphereAbstract Recent high-resolution solar observations have unveiled the presence of small-scale loop-like structures in the lower solar atmosphere, often referred to as unresolved fine structures, low-lying loops, and miniature hot loops. These structures undergo rapid changes within minutes, and their formation mechanism has remained elusive. In this study, we conducted a comprehensive analysis of two small loops utilizing data from the Interface Region Imaging Spectrograph (IRIS), the Goode Solar Telescope (GST) at Big Bear Solar Observatory, and the Atmospheric Imaging Assembly and the Helioseismic Magnetic Imager on board the Solar Dynamics Observatory, aiming to elucidate the underlying process behind their formation. The GST observations revealed that these loops, with lengths of ∼3.5 Mm and heights of ∼1 Mm, manifest as bright emission structures in Hαwing images, particularly prominent in the red wing. IRIS observations showcased these loops in 1330 Å slit-jaw images, with transition region (TR) and chromospheric line spectra exhibiting significant enhancement and broadening above the loops, indicative of plasmoid-mediated reconnection during their formation. Additionally, we observed upward-erupting jets above these loops across various passbands. Furthermore, differential emission measurement analysis reveals an enhanced emission measure at the location of these loops, suggesting the presence of plasma exceeding 1 MK. Based on our observations, we propose that these loops and associated jets align with the minifilament eruption model. Our findings suggest a unified mechanism governing the formation of small-scale loops and jets akin to larger-scale X-ray jets.more » « less
-
The trajectory of a molecular system undergoing a reversible reaction A ⇌ B and crossing and recrossing a transition state separating the reactant and product consists of loops, i.e., excursions from the transition state to either side and back to the transition state. Motivated by recent experimental observations of loops, here, we discuss some of their statistical properties. In particular, we highlight that the transition-state rate is not only an upper bound on the true reaction rate but also a physical property of the loops. We further find that loops can be unambiguously divided into two sub-ensembles. Those consist of short loops, which are brief excursions from the transition state, and long loops that get trapped in the reactant or product wells before eventually returning to the barrier. Finally, we show that the loop time distribution contains information about both the reaction rate coefficients and their transition-state-theory counterparts.more » « less
-
Abstract Understanding the mechanisms underlying nutrient (nitrogen and phosphorus) and carbon cycling in reefs is critical for effective management. Research on reef nutrient and carbon cycling needs to account for (i) the contributions of multiple organisms, (ii) abiotic and biotic drivers, and (iii) a social-ecological perspective. In this paper, we review the mechanisms underlying nutrient and carbon cycling in reef social-ecological systems and analyse them using causal loop analysis. We identify direct and indirect pathways and feedback loops through nutrient and carbon cycles that shape the dominant benthic state of reefs: coral, algal, and sponge-dominated states. We find that two of three anthropogenic impact scenarios (size-selective fishing and land use change) have primarily negative consequences for coral and macroalgae via the nutrient and carbon cycles. A third scenario (runoff) has fewer negative impacts on sponges compared to other benthos. In all scenarios, frequent positive feedback loops (size-selective fishing: 7 of 12 loops; runoff: 6 of 9 loops; land use change: 8 of 11 loops) lead to system destabilization; however, the presence of multiple loops introduces avenues whereby reefs may retain coral dominance despite anthropogenic pressures. Context-specific information on the relative strength of loops will be necessary to predict future reef state.more » « less
An official website of the United States government

