Transcriptional synergy in human aortic endothelial cells is vulnerable to combination p300/CBP and BET bromodomain inhibition.

Combinatorial signaling by proinflammatory cytokines synergizes to exacerbate toxicity to cells and tissue injury during acute infections. To explore synergism at the gene-regulatory level, we investigated the dynamics of transcription and chromatin signaling in response to dual cytokines by integrating nascent RNA imaging mass spectrometry, RNA sequencing, amplification-independent mRNA quantification, assay for transposase-accessible chromatin using sequencing (ATAC-seq), and transcription factor profiling. Costimulation with interferon-gamma (IFNγ) and tumor necrosis factor alpha (TNFα) synergistically induced a small subset of genes, including the chemokines , -, and -.

Postnatal oxytocin treatment improves survival and neurodevelopmental outcomes in an animal model of neonatal abstinence syndrome.

Prenatal exposure to drugs of abuse results in neonatal abstinence syndrome (NAS). NAS causes significant morbidity and is associated with costly and lengthy hospitalization. Current pharmacotherapy is suboptimal with no FDA approved treatments.

Nurses in Action: A Response to Cultural Care Challenges in a Pediatric Acute Care Setting.

Culturally congruent care is satisfying, meaningful, fits with people's daily lives, and promotes their health and wellbeing. A group of staff nurses identified specific clinical challenges they faced in providing such care for Hispanic and underserved Caucasian children and families in the pediatric medical-surgical unit of an urban regional children's hospital in the southeastern U.S.

Synthesis and oxidation of carboxylate-bridged diiron(II) complexes with substrates tethered to primary alkyl amine ligands.

The synthesis and crystallographic characterization of a series of diiron(II) complexes with sterically hindered terphenyl carboxylate ligands and alkyl amine donors are presented. The compounds [Fe(2)(mu-O(2)CAr(Tol))(4)(L)(2)] (L=NH(2)(CH(2))(2)SBn (1); NH(2)(CH(2))(3)SMe (2); NH(2)(CH(2))(3)CCH (3)), where (-)O(2)CAr(Tol) is 2,6-di(p-tolyl)benzoate, and [Fe(2)(mu-O(2)CAr(Xyl))(2)(O(2)CAr(Xyl))(2)(L)(2)] (L=NH(2)(CH(2))(3)SMe (4); NH(2)(CH(2))(3)CCH (5)), where (-)O(2)CAr(Xyl) is 2,6-di(3,5-dimethylphenyl)benzoate, were prepared as small molecule mimics of the catalytic sites of carboxylate-bridged non-heme diiron enzymes. The compounds with the (-)O(2)CAr(Tol) carboxylate form tetrabridged structures, but those containing the more sterically demanding (-)O(2)CAr(Xyl) ligand have only two bridging ligands.

Dioxygen-initiated oxidation of heteroatomic substrates incorporated into ancillary pyridine ligands of carboxylate-rich diiron(II) complexes.

Progress toward the development of functional models of the carboxylate-bridged diiron active site in soluble methane monooxygenase is described in which potential substrates are introduced as substituents on bound pyridine ligands. Pyridine ligands incorporating a thiol, sulfide, sulfoxide, or phosphine moiety were allowed to react with the preassembled diiron(II) complex [Fe(2)(mu-O(2)CAr(R))(2)(O(2)CAr(R))(2)(THF)(2)], where (-)O(2)CAr(R) is a sterically hindered 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh). The resulting diiron(II) complexes were characterized crystallographically.

Synthesis, characterization, and preliminary oxygenation studies of benzyl- and ethyl-substituted pyridine ligands of carboxylate-rich diiron(II) complexes.

In this study benzyl and ethyl groups were appended to pyridine and aniline ancillary ligands in diiron(II) complexes of the type [Fe(2)(mu-O(2)CAr(R))(2)(O(2)CAr(R))(2)(L)(2)], where (-)O(2)CAr(R) is a sterically hindered terphenyl carboxylate, 2,6-di(p-tolyl)- or 2,6-di(p-fluorophenyl)benzoate (R = Tol or 4-FPh, respectively). These crystallographically characterized compounds were prepared as analogues of the diiron(II) center in the hydroxylase component of soluble methane monooxygenase (MMOH). The use of 2-benzylpyridine (2-Bnpy) yielded doubly bridged [Fe(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(2-Bnpy)(2)] (1) and [Fe(2)(mu-O(2)CAr(4)(-)(FPh))(2)(O(2)CAr(4)(-)(FPh))(2)(2-Bnpy)(2)] (4), whereas tetra-bridged [Fe(2)(mu-O(2)CAr(Tol))(4)(4-Bnpy)(2)] (3) resulted when 4-benzylpyridine (4-Bnpy) was employed.

Oxidation of sulfide, phosphine, and benzyl substrates tethered to N-donor pyridine ligands in carboxylate-bridged diiron(II) complexes.

Substituted pyridines were employed to prepare a series of terphenylcarboxylate-bridged diiron(II) compounds to mimic aspects of the chemistry at the active sites of bacterial multicomponent monooxygenases, including soluble methane monooxygenase (sMMO) and toluene monooxygenase (ToMO). Complexes of general formula [Fe2(O2CArTol)4L], L = 2, 3, or 4-pyridyldiphenylphosphine, 2-pyridylphenylsulfide, or 2-benzylpyridine and ArTol = 2,6-di(p-tolyl)benzoate, were synthesized and characterized by X-ray crystallography. Upon exposure of these compounds to dioxygen, ligand oxidation ensued and, in one case, proceeded catalytically.