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  1. 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. 
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    Free, publicly-accessible full text available June 13, 2024
  2. Abstract

    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.

     
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  3. 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. 
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  4. Abstract

    Meiosis in the budding yeast Saccharomyces cerevisiae is used to create haploid yeast spores from a diploid mother cell. During meiosis II, cytokinesis occurs by closure of the prospore membrane, a membrane that initiates at the spindle pole body and grows to surround each of the haploid meiotic products. Timely prospore membrane closure requires SPS1, which encodes an STE20 family GCKIII kinase. To identify genes that may activate SPS1, we utilized a histone phosphorylation defect of sps1 mutants to screen for genes with a similar phenotype and found that cdc15 shared this phenotype. CDC15 encodes a Hippo-like kinase that is part of the mitotic exit network. We find that Sps1 complexes with Cdc15, that Sps1 phosphorylation requires Cdc15, and that CDC15 is also required for timely prospore membrane closure. We also find that SPS1, like CDC15, is required for meiosis II spindle disassembly and sustained anaphase II release of Cdc14 in meiosis. However, the NDR-kinase complex encoded by DBF2/DBF20MOB1 which functions downstream of CDC15 in mitotic cells, does not appear to play a role in spindle disassembly, timely prospore membrane closure, or sustained anaphase II Cdc14 release. Taken together, our results suggest that the mitotic exit network is rewired for exit from meiosis II, such that SPS1 replaces the NDR-kinase complex downstream of CDC15.

     
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  5. Abstract

    Despite having offered important hydroclimatic insights, streamflow reconstructions still see limited use in water resources operations, because annual reconstructions are not suitable for decisions at finer time scales. The few attempts toward sub‐annual reconstructions have relied on statistical disaggregation, which uses none or little proxy information. Here, we develop a novel framework that optimizes proxy combinations to simultaneously produce seasonal and annual reconstructions. Importantly, the framework ensures that total seasonal flow matches annual flow closely. This mass balance criterion is necessary to avoid misguiding water management decisions, such as the allocation of water rights or dam release decisions. Using the framework, and leveraging a multi‐species network of ring width and celluloseO in Southeast Asia, we reconstruct seasonal and annual inflow to Thailand's largest reservoir. The reconstructions are statistically skillful. Furthermore, they preserve the mass balance well: the differences are mostly within 10% of the mean annual flow. As a result, the reconstructions provide more reliable estimates of the seasonal and annual surface water availability. This work is one step closer toward operational usability of streamflow reconstruction in water resources management.

     
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