Teleost TRAF7, a protein functions in the host antiviral responses via NF-κB and IRF3/7 mediated signaling

Tumor necrosis factor receptor-associated factors (TRAFs) play vital roles in tumor necrosis factor receptor (TNF-R) and interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) mediated signaling pathway. However, the role that TRAF7 plays in the host immune responses is largely unknown in comparison to the extensive and in-depth research that has been conducted on other members of the TRAF family. Notably, Lc-TRAF7, a cloned TRAF7 ortholog, was discovered in the large yellow croaker (Larimichthys crocea) in the current study, which has an open reading frame (ORF) of 1,962 base pairs and encodes a protein of 653 amino acids (aa). Lc-TRAF7 is consisted of a RING finger domain, a coiled-coil domain, and seven WD40 domains, with the genomic organization consisted of 20 exons and 19 introns. According to the expression analysis, Lc-TRAF7 was presented in a wide range of detected organs and tissues of the healthy fish, and was able to significantly induced by stimulations of poly I:C, LPS, PGN, and Pseudomonas plecoglossicida infection. Subcellular distribution analysis revealed that Lc-TRAF7 was a cytoplasmic protein, with the RING finger and coiled-coil domain function importantly in its subcellular localization. Luciferase assays demonstrated that Lc-TRAF7 overexpression significantly induced the activation of NF-κB, IRF3, IRF7, and IFN1 promoters. In addition, the WD40 domains play a pivotal role in the NF-κB promoter activation, whereas the RING finger and coiled-coil domain were essential in the IRF3, IRF7, and IFN1 promoter activation. Notably, Lc-TRAF7 overexpression could suppress SVCV proliferation in EPC cells, and the expression levels of IRF3, IRF7, ISG15, ISG56, RSAD2, and TNF-α were up-regulated under Lc-TRAF7 overexpression in LYCMS cells. These findings collectively implied that Lc-TRAF7 may function as an important regulator in the host antiviral responses via the NF-κB as well as IRF3/7 involved signaling pathways

Direct Lineage Conversion of Adult Mouse Liver Cells and B Lymphocytes to Neural Stem Cells

SummaryOverexpression of transcription factors has been used to directly reprogram somatic cells into a range of other differentiated cell types, including multipotent neural stem cells (NSCs), that can be used to generate neurons and glia. However, the ability to maintain the NSC state independent of the inducing factors and the identity of the somatic donor cells remain two important unresolved issues in transdifferentiation. Here we used transduction of doxycycline-inducible transcription factors to generate stable tripotent NSCs. The induced NSCs (iNSCs) maintained their characteristics in the absence of exogenous factor expression and were transcriptionally, epigenetically, and functionally similar to primary brain-derived NSCs. Importantly, we also generated tripotent iNSCs from multiple adult cell types, including mature liver and B cells. Our results show that self-maintaining proliferative neural cells can be induced from nonectodermal cells by expressing specific combinations of transcription factors

Genome-wide determination of drug localization

A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide new and important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods provide a powerful approach to enhance understanding of therapeutic action and characterize the specificity of chemical entities that interact with DNA or genome-associated proteins

Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency

Embryonic stem cells (ESCs) of mice and humans have distinct molecular and biological characteristics, raising the question of whether an earlier, “naive” state of pluripotency may exist in humans. Here we took a systematic approach to identify small molecules that support self-renewal of naive human ESCs based on maintenance of endogenous OCT4 distal enhancer activity, a molecular signature of ground state pluripotency. Iterative chemical screening identified a combination of five kinase inhibitors that induces and maintains OCT4 distal enhancer activity when applied directly to conventional human ESCs. These inhibitors generate human pluripotent cells in which transcription factors associated with the ground state of pluripotency are highly upregulated and bivalent chromatin domains are depleted. Comparison with previously reported naive human ESCs indicates that our conditions capture a distinct pluripotent state in humans that closely resembles that of mouse ESCs. This study presents a framework for defining the culture requirements of naive human pluripotent cells.Simons Foundation (Grant SFLIFE 286977)National Institutes of Health (U.S.) (Grant RO1-CA084198)National Science Foundation (U.S.). Graduate Research FellowshipJerome and Florence Brill Graduate Student Fellowshi

Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs during Differentiation and Regeneration

SummaryBMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity

Dirac semimetal PdTe2 temperature-dependent quasiparticle dynamics and electron-phonon coupling

Dirac semimetal PdTe2 single-crystal temperature-dependent ultrafast carrier and phonon dynamics were studied using ultrafast optical pump-probe spectroscopy. Two distinct carrier and coherent phonons relaxation processes were identified in the 5 K - 300 K range. Quantitative analysis revealed a fast relaxation process ({\tau}_f) occurring on a subpicosecond time scale which originated from electron-phonon thermalization. This was followed by a slower relaxation process ({\tau}_s) with a time scale of ~ 7-9.5 ps which originated from phonon-assisted electron-hole recombination. Two significant vibrational modes resolved at all measured temperatures and corresponded to Te atoms in-plane (E_g), and out-of-plane (A_1g), motion. As temperature increased both phonon modes softened markedly. A_1g mode frequency monotonically decreased as temperature increased. Its damping rate remained virtually unchanged. As expected, E_g decreased uniformly as temperatures rose. At temperatures above 80 K, there was insignificant change. Test results suggested that pure dephasing played an important role in the relaxation processes. PdTe2 phonon is thought responsible for its superconductive properties. Examining phonons behavior should improve the understanding of its complex superconductivity.Comment: 6 pages, 4 figure

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study

Background and AimsThe association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study.MethodsWe included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia.ResultsAfter adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1.ConclusionHigher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women