The historically recent domestication of fishes has been essential to meet the protein demands of a growing human population. Selection for traits of interest during domestication is a complex process whose epigenetic basis is poorly understood. Cytosine hydroxymethylation is increasingly recognized as an important DNA modification involved in epigenetic regulation. In the present study, we investigated if hydroxymethylation plays a role in fish domestication and demonstrated for the first time at a genome-wide level and single nucleotide resolution that the muscle hydroxymethylome changes after a single generation of Nile tilapia (Oreochromis niloticus, Linnaeus) domestication. The overall decrease in hydroxymethylcytosine levels was accompanied by the downregulation of 2015 genes in fish reared in captivity compared to their wild progenitors. In contrast, several myogenic and metabolic genes that can affect growth potential were upregulated. There were 126 differentially hydroxymethylated cytosines between groups, which were not due to genetic variation; they were associated with genes involved in immune-, growth- and neuronal-related pathways. Taken together, our data unveil a new role for DNA hydroxymethylation in epigenetic regulation of fish domestication with impact in aquaculture and implications in artificial selection, environmental adaptation and genome evolution.Calcium (Ca2+) as a universal signal molecule plays pivotal roles in plant growth and development. It regulates root morphogenesis mainly through mediating phytohormone and stress signalings or affecting these signalings. In recent years, much progress has been made in understanding the roles of Ca2+ in primary root development. Here, we summarize recent advances in the functions and mechanisms of Ca2+ in modulating primary root growth in plants under normal and stressful conditions.In the past decade, the relevance of antibodies as therapeutics has increased substantially. Therefore, structural and functional characterization, in particular of the complementarity-determining regions (CDRs), is crucial to the design and engineering of antibodies with unique binding properties. Various studies have focused on classifying the CDR loops into a small set of main-chain conformations to facilitate antibody design by assuming that certain sequences can only adopt a limited number of conformations. Here, we present a kinetic classification of CDR loop structures as ensembles in solution. Using molecular dynamics simulations in combination with strong experimental structural information, we observe conformational transitions between canonical clusters and additional dominant solution structures in the micro-to-millisecond timescale for all CDR loops, independent of length and sequence composition. Besides identifying all relevant conformations in solution, our results revealed that various canonical cluster medians actually belong to the same kinetic minimum. Additionally, we reconstruct the kinetics and probabilities of the conformational transitions between canonical clusters, and thereby extend the model of static canonical structures to reveal a dynamic conformational ensemble in solution as a new paradigm in the field of antibody structure design.Abbreviations CDR Complementary-determining region; Fv Antibody variable fragment; PCCA Perron cluster analysis; tICA Time-lagged independent component analysis; VH Heavy chain variable region; VL Light chain variable region.Finlets are a series of small non-retractable fins common to scombrid fishes (mackerels, bonitos and tunas), which are known for their high swimming speed. It is hypothesized that these small fins could potentially affect propulsive performance. Here, we combine experimental and computational approaches to investigate the hydrodynamics of finlets in yellowfin tuna (Thunnus albacares) during steady swimming. High-speed videos were obtained to provide kinematic data on the in vivo motion of finlets. High-fidelity simulations were then carried out to examine the hydrodynamic performance and vortex dynamics of a biologically realistic multiple-finlet model with reconstructed kinematics. It was found that finlets undergo both heaving and pitching motion and are delayed in phase from anterior to posterior along the body. Simulation results show that finlets were drag producing and did not produce thrust. The interactions among finlets helped reduce total finlet drag by 21.5%. Pitching motions of finlets helped reduce the power consumed by finlets during swimming by 20.8% compared with non-pitching finlets. Moreover, the pitching finlets created constructive forces to facilitate posterior body flapping. Wake dynamics analysis revealed a unique vortex tube matrix structure and cross-flow streams redirected by the pitching finlets, which supports their hydrodynamic function in scombrid fishes. Limitations on modelling and the generality of results are also discussed.BACKGROUND Escherichia coli ST131, mainly its H30 clade, is the leading cause of extraintestinal E. coli infections but its correlates of virulence are undefined. MATERIALS AND METHODS We tested in a murine sepsis model 84 ST131 isolates that differed by country of origin (Spain vs. USA), clonal subset, resistance markers, and virulence genes (VGs). Virulence outcomes, including illness severity score (ISS) and "killer" status (>80% mouse lethality), were compared statistically with clonal subset, individual and combined VGs, molecularly defined extraintestinal and uropathogenic E. coli (ExPEC, UPEC) status, and country of origin. RESULTS Virulence varied widely by strain. Univariable correlates of median ISS and percent "killer" (outcomes if variable present vs. absent) included pap (ISS, 4.4 vs. 3.8; "killer", 71% vs. 46%), kpsMII (4.1 vs. 2.3; 59% vs. 25%), K2/K100 (4.4 vs. 3.2; 77% vs.  https://www.selleckchem.com/products/VX-745.html  41%), ExPEC (4.2 vs. 2.2; 62% vs. 17%), Spanish origin (4.3 vs. 3.1; 65% vs. 36%), and H30R1 subset (2.5 vs. 4.1; 35% vs. 59%). With multivariable adjustment, ExPEC status was the only consistently significantly predictive variable. CONCLUSION Within ST131 the strongest predictor of experimental virulence was molecularly defined ExPEC status. Clonal subsets seemed to behave differently in the murine sepsis model by country of origin.