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Low-complexity nucleotide repeat sequences, which are implicated in several neurological disorders, undergo liquid–liquid phase separation (LLPS) provided the number of repeat units, n , exceeds a critical value. Here, we establish a link between the folding landscapes of the monomers of trinucleotide repeats and their propensity to self-associate. Simulations using a coarse-grained Self-Organized Polymer (SOP) model for (CAG) n repeats in monovalent salt solutions reproduce experimentally measured melting temperatures, which are available only for small n . By extending the simulations to large n , we show that the free-energy gap, ΔG S , between the ground state (GS) and slipped hairpin (SH) states is a predictor of aggregation propensity. The GS for even n is a perfect hairpin (PH), whereas it is a SH when n is odd. The value of ΔG S (zero for odd n ) is larger for even n than for odd n . As a result, the rate of dimer formation is slower in (CAG) 30 relative to (CAG) 31 , thus linking ΔG S to RNA–RNA association. The yield of the dimer decreases dramatically, compared to the wild type, in mutant sequences in which the population of the SH decreases substantially. Association between RNA chains is preceded by a transition to the SH even if the GS is a PH. The finding that the excitation spectrum—which depends on the exact sequence, n , and ionic conditions—is a predictor of self-association should also hold for other RNAs (mRNA for example) that undergo LLPS. 

In many countries, water distribution systems consist of large, highly pressurized pipe networks that require an excessive amount of energy and that are vulnerable to large-scale contamination. To imagine the future of water distribution, we can learn from Hanoi, Vietnam, where water is distributed at low pressures and most buildings are equipped with a basement tank, a rooftop tank, and separate water treatment processes, resulting in a system that consumes less energy and that is more resilient.

 

Water system operations require subannual streamflow data—e.g., monthly or weekly—that are not readily achievable with conventional streamflow reconstructions from annual tree rings. This mismatch is particularly relevant to highly seasonal rivers such as Thailand's Chao Phraya. Here, we combine tree ring width and stable oxygen isotope ratios (δ¹⁸O) from Southeast Asia to produce 254‐year, monthly‐resolved reconstructions for all four major tributaries of the Chao Phraya. From the reconstructions, we derive subannual streamflow indices to examine past hydrological droughts and pluvials, and find coherence and heterogeneity in their histories. The monthly resolution reveals the spatiotemporal variability in wet season timing, caused by interactions between early summer typhoons, monsoon rains, catchment location, and topography. Monthly‐resolved reconstructions, like the ones presented here, not only broaden our understanding of past hydroclimatic variability, but also provide data that are functional to water management and climate‐risk analyses, a significant improvement over annual reconstructions.

 

Massive black holes (BHs) at the centres of massive galaxies are ubiquitous. The population of BHs within dwarf galaxies, on the other hand, is evasive. Dwarf galaxies are thought to harbour BHs with proportionally small masses, including intermediate mass BHs, with masses 102 more » « less

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RNA molecules cannot fold in the absence of counterions. Experiments are typically performed in the presence of monovalent and divalent cations. How to treat the impact of a solution containing a mixture of both ion types on RNA folding has remained a challenging problem for decades. By exploiting the large concentration difference between divalent and monovalent ions used in experiments, we develop a theory based on the reference interaction site model (RISM), which allows us to treat divalent cations explicitly while keeping the implicit screening effect due to monovalent ions. Our theory captures both the inner shell and outer shell coordination of divalent cations to phosphate groups, which we demonstrate is crucial for an accurate calculation of RNA folding thermodynamics. The RISM theory for ion–phosphate interactions when combined with simulations based on a transferable coarse-grained model allows us to predict accurately the folding of several RNA molecules in a mixture containing monovalent and divalent ions. The calculated folding free energies and ion-preferential coefficients for RNA molecules (pseudoknots, a fragment of the rRNA, and the aptamer domain of the adenine riboswitch) are in excellent agreement with experiments over a wide range of monovalent and divalent ion concentrations. Because the theory is general, it can be readily used to investigate ion and sequence effects on DNA properties.