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SEquence Evaluation throughk-mer Representation (SEEKR) is a method of sequence comparison that uses sequence substrings calledk-mers to quantify the nonlinear similarity between nucleic acid species. We describe the development of new functions within SEEKR that enable end-users to estimateP-values that ascribe statistical significance to SEEKR-derived similarities, as well as visualize different aspects ofk-mer similarity. We apply the new functions to identify chromatin-enriched lncRNAs that containXIST-like sequence features, and we demonstrate the utility of applying SEEKR on lncRNA fragments to identify potential RNA-protein interaction domains. We also highlight ways in which SEEKR can be applied to augment studies of lncRNA conservation, and we outline the best practice of visualizing RNA-seq read density to evaluate support for lncRNA annotations before their in-depth study in cell types of interest. 

Stanniocalcin 1 (Stc1) is well known for its role in regulating calcium uptake in fish by acting on ionocytes or NaR cells. A hallmark of NaR cells is the expression of Trpv6, a constitutively open calcium channel. Recent studies in zebrafish suggest that genetical deletion of Stc1a and Trpv6 individually both increases IGF signaling and NaR cell proliferation. Whiletrpv6^-/-fish suffered from calcium deficiency and died prematurely,stc1a^-/-fish had elevated body calcium levels but also died prematurely. The relationship between Stc1a, Trpv6, and IGF signaling in regulating calcium homeostasis and organismal survival is unclear. Here we report that loss of Stc1a increases Trpv6 expression in NaR cells in an IGF signaling-dependent manner. Treatment with CdCl₂, a Trpv6 inhibitor, reduced NaR cell number instc1a^-/-fish to the sibling levels. Genetic and biochemical analysis results suggest that Stc1a and Trpv6 regulate NaR cell proliferation via the same IGF pathway. Alizarin red staining detected abnormal calcium deposits in the yolk sac region and kidney stone-like structures instc1a^-/-fish. Double knockout or pharmacological inhibition of Trpv6 alleviated these phenotypes, suggesting that Stc1a inhibit epithelial Ca²⁺uptake by regulating Trpv6 expression and activity.stc1a^-/-mutant fish developed cardiac edema, body swelling, and died prematurely. Treatment ofstc1a^-/-fish with CdCl₂or double knockout of Trpv6 alleviated these phenotypes. These results provide evidence that Stc1a regulates calcium homeostasis and organismal survival by suppressing Trpv6 expression and inhibiting IGF signaling in ionocytes. 

Molecular dynamic (MD) simulations are used to probe molecular systems in regimes not accessible to physical experiments. A common goal of these simulations is to compute the power spectral density (PSD) of some component of the system such as particle velocity. In certain MD simulations, only a few time locations are observed, which makes it difficult to estimate the autocorrelation and PSD. This work develops a novel nuclear norm minimization-based method for this type of sub-sampled data, based on a parametric representation of the PSD as the sum of Lorentzians. We show results on both synthetic data and a test system of methanol. 

The molecular mechanisms regulating cell quiescence-proliferation balance are not well defined. Using a zebrafish model, we report that Stc1a, a secreted glycoprotein, plays a key role in regulating the quiescence-proliferation balance of Ca²⁺transporting epithelial cells (ionocytes). Zebrafishstc1a, but not the otherstcgenes, is expressed in a Ca²⁺state-dependent manner. Genetic deletion ofstc1a, but notstc2b, increased ionocyte proliferation, leading to elevated body Ca²⁺levels, cardiac edema, body swelling, and premature death. The increased ionocyte proliferation was accompanied by an increase in the IGF1 receptor-mediated PI3 kinase-Akt-Tor signaling activity in ionocytes. Inhibition of the IGF1 receptor, PI3 kinase, Akt, and Tor signaling reduced ionocyte proliferation and rescued the edema and premature death instc1a^–/–fish, suggesting that Stc1a promotes ionocyte quiescence by suppressing local IGF signaling activity. Mechanistically, Stc1 acts by inhibiting Papp-aa, a zinc metalloproteinase degrading Igfbp5a. Inhibition of Papp-aa proteinase activity restored ionocyte quiescence-proliferation balance. Genetic deletion ofpapp-aaor its substrateigfbp5ain thestc1a^–/–background reduced ionocyte proliferation and rescued the edema and premature death. These findings uncover a novel and Ca²⁺state-dependent pathway regulating cell quiescence. Our findings also provide new insights into the importance of ionocyte quiescent-proliferation balance in organismal Ca²⁺homeostasis and survival.