Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression

The transcription factor LSF is highly expressed in hepatocellular carcinoma (HCC) and promotes oncogenesis. Factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity and exerts anti-proliferative activity. Here, we show that LSF binds directly to the maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1) and its accessory protein UHRF1 both in vivo and in vitro. Binding of LSF to DNMT1 stimulated DNMT1 activity and FQI1 negated the methyltransferase activation. Addition of FQI1 to the cell culture disrupted LSF bound DNMT1 and UHRF1 complexes, resulting in global aberrant CpG methylation. Differentially methylated regions (DMR) containing at least 3 CpGs, were significantly altered by FQI1 compared to control cells. The DMRs were mostly concentrated in CpG islands, proximal to transcription start sites, and in introns and known genes. These DMRs represented both hypo and hypermethylation, correlating with altered gene expression. FQI1 treatment elicits a cascade of effects promoting altered cell cycle progression. These findings demonstrate a novel mechanism of FQI1 mediated alteration of the epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression.We would like to thank Drs. Donald Comb, Rich Roberts, William Jack and Clotilde Carlow at New England Biolabs Inc. for research support and encouragement. The authors thank Dr. Lauren Brown (Boston University Center for Molecular Discovery) for the preparation of FQI1. UH research on this project was supported by Ignition Awards from Boston University and a Johnson & Johnson Clinical Innovator's Award through Boston University. SES research is supported by the NIH (P50 GM067041 & R24 GM111625). Research performed by HGC was partly a requirement for the MCBB graduate program at Boston University and supported by NEB. (Boston University; Johnson & Johnson Clinical Innovator's Award through Boston University; P50 GM067041 - NIH; R24 GM111625 - NIH; NEB)Published versio

Quantum dynamics in photonic crystals

Employing a recently developed method that is numerically accurate within a model space simulating the real-time dynamics of few-body systems interacting with macroscopic environmental quantum fields, we analyze the full dynamics of an atomic system coupled to a continuum light-field with a gapped spectral density. This is a situation encountered, for example, in the radiation field in a photonic crystal, whose analysis has been so far been confined to limiting cases due to the lack of suitable numerical techniques. We show that both atomic population and coherence dynamics can drastically deviate from the results predicted when using the rotating wave approximation, particularly in the strong coupling regime. Experimental conditions required to observe these corrections are also discussed.Comment: 5 pages, 2 figures Updated with published versio

N′-[(E)-4-Chloro­benzyl­idene]-2-(4-isobutyl­phen­yl)propanohydrazide

The asymmetric unit of title compound, C20H23ClN2O, consists of two crystallographically independent mol­ecules (A and B) in which the orientations of the 4-isobutyl­phenyl units are different. The isobutyl group of mol­ecule B is disordered over two positions with occupancies of 0.850 (5) and 0.150 (5). The dihedral angle between the two benzene rings is 88.70 (9)° in mol­ecule A and 89.38 (9)° in mol­ecule B. The independent mol­ecules are linked together into chains along [100] by N—H⋯O and C—H⋯O hydrogen bonds, and by C—H⋯π inter­actions. In the chain, N—H⋯O and C—H⋯O hydrogen bonds generate R 2 1(6) ring motifs. In addition, C—H⋯N hydrogen bonds are observed. The presence of pseudosymmetry in the structure suggests the higher symmetry space group Pbca but attempts to refine the structure in this space group resulted in high R (0.119) and wR (0.296) values

An implantable compound-releasing capsule triggered on demand by ultrasound

Implantable devices have a large potential to improve human health, but they are often made of biofouling materials that necessitate special coatings, rely on electrical connections for external communication, and require a continuous power source. This paper demonstrates an alternative platform, which we call iTAG (implantable thermally actuated gel), where an implanted capsule can be wirelessly controlled by ultrasound to trigger the release of compounds. We constructed a millimetersized capsule containing a co-polymer gel (NiPAAm-co-AAm) that contracts above body temperature (i.e. at 45°C) to release compounds through an opening. This gel-containing capsule is biocompatible and free of toxic electronic or battery components. An ultrasound hardware, with a focused ultrasound (FUS) transducer and a co-axial A-mode imaging transducer, was used to image the capsule (to monitor in real time its position, temperature, and effectiveness of dose delivery), as well as to trigger a rapid local rise in temperature, contraction of gel, and release of compounds in vitro and in vivo. The combination of this gel-based capsule and compact ultrasound hardware can serve as a platform for triggering local release of compounds, including potentially in deep tissue, to achieve tailored personalized therapy

Observation of an Efimov resonance in an ultracold mixture of atoms and weakly bound dimers

We discuss our recent observation of an atom-dimer Efimov resonance in an ultracold mixture of Cs atoms and Cs_2 Feshbach molecules [Nature Phys. 5, 227 (2009)]. We review our experimental procedure and present additional data involving a non-universal g-wave dimer state, to contrast our previous results on the universal s-wave dimer. We resolve a seeming discrepancy when quantitatively comparing our experimental findings with theoretical results from effective field theory.Comment: Conference Proceeding ICPEAC 2009 Kalamazoo, to appear in Journal of Physics: Conference Serie

Observation of an Efimov resonance in an ultracold mixture of atoms and weakly bound dimers

We discuss our recent observation of an atom-dimer Efimov resonance in an ultracold mixture of Cs atoms and Cs_2 Feshbach molecules [Nature Phys. 5, 227 (2009)]. We review our experimental procedure and present additional data involving a non-universal g-wave dimer state, to contrast our previous results on the universal s-wave dimer. We resolve a seeming discrepancy when quantitatively comparing our experimental findings with theoretical results from effective field theory.Comment: Conference Proceeding ICPEAC 2009 Kalamazoo, to appear in Journal of Physics: Conference Serie

Observation of an Efimov resonance in an ultracold mixture of atoms and weakly bound dimers

We discuss our recent observation of an atom-dimer Efimov resonance in an ultracold mixture of Cs atoms and Cs_2 Feshbach molecules [Nature Phys. 5, 227 (2009)]. We review our experimental procedure and present additional data involving a non-universal g-wave dimer state, to contrast our previous results on the universal s-wave dimer. We resolve a seeming discrepancy when quantitatively comparing our experimental findings with theoretical results from effective field theory.Comment: Conference Proceeding ICPEAC 2009 Kalamazoo, to appear in Journal of Physics: Conference Serie