RESULTS Relative to CWF (2011 and 2016), no CWF (2011 and 2016) was associated with increased dental ASH rates in children aged 0-4 [incidence rate ratio (IRR) = 1.171 (95% confidence interval 1.064, 1.288)] and aged 5-12 years [IRR = 1.181 (1.084, 1.286)]. An interaction between area-level deprivation and CWF showed that the association between CWF and dental ASH rates was greatest within the most deprived quintile of children aged 0-4 years [IRR = 1.316 (1.052, 1.645)]. CONCLUSIONS CWF was associated with a reduced dental ASH rate for children aged 0-4 and 5-12 years. Children living in the most deprived areas showed the greatest effect of CWF on dental ASH rates, indicating that the greater health gain from CWF occurred for those with the highest socio-economic disadvantage. Variation in CWF contributes to structural inequities in oral-health outcomes for children. © The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.As species recover from exploitation, continued assessments of connectivity and population structure are warranted to provide information for conservation and management. This is particularly true in species with high dispersal capacity, such as migratory whales, where patterns of connectivity could change rapidly. Here we build on a previous long-term, large-scale collaboration on southern right whales (Eubalaena australis) to combine new (nnew) and published (npub) mitochondrial (mtDNA) and microsatellite genetic data from all major wintering grounds and, uniquely, the South Georgia (Islas Georgias del Sur SG) feeding grounds. Specifically, we include data from Argentina (npub mtDNA/microsatellite=208/46), Brazil (nnew mtDNA/microsatellite=50/50), South Africa (nnew mtDNA/microsatellite=66/77, npub mtDNA/microsatellite=350/47), Chile-Peru (nnew mtDNA/microsatellite=1/1), the Indo-Pacific (npub mtDNA/microsatellite=769/126), and SG (npub mtDNA/microsatellite=8/0, nnew mtDNA/microsatellite=3/11) to investigate the position of previously unstudied habitats in the migratory network Brazil, SG and Chile-Peru. These new genetic data show connectivity between Brazil and Argentina, exemplified by weak genetic differentiation and the movement of one genetically identified individual between the South American grounds. The single sample from Chile-Peru had a mtDNA haplotype previously only observed in the Indo-Pacific and had a nuclear genotype that appeared admixed between the Indo-Pacific and South Atlantic, based on genetic clustering and assignment algorithms. The SG samples were clearly South Atlantic, and were more similar to the South American than the South African wintering grounds. This study highlights how international collaborations are critical to provide context for emerging or recovering regions, like the SG feeding ground, as well as those that remain critically endangered, such as Chile-Peru. © The American Genetic Association 2020.Structural DNA nanotechnology, as exemplified by DNA origami, has enabled the design and construction of molecularly-precise objects for a myriad of applications. However, limitations in imaging, and other characterization approaches, make a quantitative understanding of the folding process challenging.  https://www.selleckchem.com/  Such an understanding is necessary to determine the origins of structural defects, which constrain the practical use of these nanostructures. Here, we combine careful fluorescent reporter design with a novel affine transformation technique that, together, permit the rigorous measurement of folding thermodynamics. This method removes sources of systematic uncertainty and resolves problems with typical background-correction schemes. This in turn allows us to examine entropic corrections associated with folding and potential secondary and tertiary structure of the scaffold. Our approach also highlights the importance of heat-capacity changes during DNA melting. In addition to yielding insight into DNA origami folding, it is well-suited to probing fundamental processes in related self-assembling systems. Published by Oxford University Press on behalf of Nucleic Acids Research 2020.DNA double-strand breaks are repaired by end-joining or homologous recombination. A key-committing step of recombination is DNA end resection. In resection, phosphorylated CtIP first promotes the endonuclease of MRE11-RAD50-NBS1 (MRN). Subsequently, CtIP also stimulates the WRN/BLM-DNA2 pathway, coordinating thus both short and long-range resection. The structure of CtIP differs from its orthologues in yeast, as it contains a large internal unstructured region. Here, we conducted a domain analysis of CtIP to define the function of the internal region in DNA end resection. We found that residues 350-600 were entirely dispensable for resection in vitro. A mutant lacking these residues was unexpectedly more efficient than full-length CtIP in DNA end resection and homologous recombination in vivo, and consequently conferred resistance to lesions induced by the topoisomerase poison camptothecin, which require high MRN-CtIP-dependent resection activity for repair. This suggested that the internal CtIP region, further mapped to residues 550-600, may mediate a negative regulatory function to prevent over resection in vivo. The CtIP internal deletion mutant exhibited sensitivity to other DNA-damaging drugs, showing that upregulated resection may be instead toxic under different conditions. These experiments together identify a region within the central CtIP domain that negatively regulates DNA end resection. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.BACKGROUND Lymphocyte activation gene-3 (LAG-3) is one of the immune checkpoint molecules, negatively regulating the T cell reactions. The present study investigated the role of LAG-3 in sepsis-induced T lymphocytes disability. METHODS Mice sepsis was induced by cecal ligation and puncture (CLP). LAG-3 expression on some immune cells were detected 24h after CLP. LAG-3-knockout mice and anti-LAG-3 antibody were applied to investigate the effects on the survival, bacterial clearance. Cytokines level, T cell counts and apoptosis (blood/spleen/thymus) were also determined. In vitro T cells apoptosis, IFN-γ secretion, proliferation were detected. IL-2 receptor (IL-2R) on T cells was also determined after CLP. RESULTS LAG-3 upregulated on CD4+/CD8+ T, CD19+ B, NK, CD4+ CD25+ Treg cells and DCs. Both LAG-3-knockout and anti-LAG-3 antibody had a positive effect on the survival, blood/peritoneal bacterial clearance in CLP mice. Cytokines level and T cells apoptosis decreased in anti-LAG-3 antibody-treated mice. Induced T cells apoptosis decreased while the IFN-γ secretion and proliferation were improved by anti-LAG-3 antibody in vitro.