Depletion of COPI in cancer cells: the role of reactive oxygen species in the induction of lipid accumulation, noncanonical lipophagy and apoptosis.

The coatomer protein complex 1 (COPI) is a multisubunit complex that coats intracellular vesicles and is involved in intracellular protein trafficking. Recently we and others found that depletion of COPI complex subunits zeta (COPZ1) and delta (ARCN1) preferentially kills tumor cells relative to normal cells. Here we delineate the specific cellular effects and sequence of events of COPI complex depletion in tumor cells.

Genomic variation in captive deer mouse (Peromyscus maniculatus) populations.

Background: Deer mice (genus Peromyscus) are the most common rodents in North America. Despite the availability of reference genomes for some species, a comprehensive database of polymorphisms, especially in those maintained as living stocks and distributed to academic investigators, is missing. In the present study we surveyed two populations of P.

Precision measurement of the neutral pion lifetime.

The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process.

A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r. In 2010, a new method using muonic hydrogen atoms found a substantial discrepancy compared with previous results, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved.

First Measurement of Near-Threshold J/ψ Exclusive Photoproduction off the Proton.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8  GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment.

Measurements of Nonsinglet Moments of the Nucleon Structure Functions and Comparison to Predictions from Lattice QCD for Q^{2}=4 GeV^{2}.

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments.

Identification of novel cancer therapeutic targets using a designed and pooled shRNA library screen.

Targeted cancer therapeutics aim to exploit tumor-specific, genetic vulnerabilities specifically affecting neoplastic cells without similarly affecting normal cells. Here we performed sequencing-based screening of an shRNA library on a panel of cancer cells of different origins as well as normal cells. The shRNA library was designed to target a subset of genes previously identified using a whole genome screening approach.

Purification of high-quality RNA from synthetic polyethylene glycol-based hydrogels.

Polyethylene glycol (PEG)-based hydrogels, with variable stiffness, are widely used in tissue engineering to investigate substrate stiffness effects on cell properties. Transcriptome analysis is a critical method for understanding cell physiology. However, significant RNA degradation was observed during the process of isolating and purifying RNA from cells encapsulated in the PEG hydrogel, thereby precluding purification of high-quality RNA.

[Long-term dental interventions in mentally retarded children under general anesthesia with sevoflurane].

Dental procedures in mentally retarded children is challenging for both dentist and for anesthesiologist. The aim of the study was to evaluate the efficacy and safety of dental care procedures under general anesthesia with sevoflurane by means of laryngeal mask in mentally retarded children. The randomized controlled study included 65 mentally retarded children with ASA 2-3 who underwent dental treatment.

[Use of analgesia and sedation in dental implantology in patients with concomitant hypertension].

Dental implants surgery in patients with hypertension increases the risk of vascular complications. The aim of the study was to examine the effect of analgesia and sedation on blood pressure and postoperative pain in dental implantology. In 76 patients with hypertension implant surgery was performed under local anesthesia only (40 patients) or under local anesthesia with propofol sedation and pre-emptive analgesia with ketorolac (36 patients).

Observation of the (Λ)(7)He hypernucleus by the (e, e'K+) reaction.

An experiment with a newly developed high-resolution kaon spectrometer and a scattered electron spectrometer with a novel configuration was performed in Hall C at Jefferson Lab. The ground state of a neutron-rich hypernucleus, (Λ)(7)He, was observed for the first time with the (e, e'K+) reaction with an energy resolution of ~0.6 MeV.

Core circadian protein CLOCK is a positive regulator of NF-κB-mediated transcription.

The circadian clock controls many physiological parameters including immune response to infectious agents, which is mediated by activation of the transcription factor NF-κB. It is widely accepted that circadian regulation is based on periodic changes in gene expression that are triggered by transcriptional activity of the CLOCK/BMAL1 complex. Through the use of a mouse model system we show that daily variations in the intensity of the NF-κB response to a variety of immunomodulators are mediated by core circadian protein CLOCK, which can up-regulate NF-κB-mediated transcription in the absence of BMAL1; moreover, BMAL1 counteracts the CLOCK-dependent increase in the activation of NF-κB-responsive genes.

Search for a new gauge boson in electron-nucleus fixed-target scattering by the APEX experiment.

We present a search at the Jefferson Laboratory for new forces mediated by sub-GeV vector bosons with weak coupling α' to electrons. Such a particle A' can be produced in electron-nucleus fixed-target scattering and then decay to an e + e- pair, producing a narrow resonance in the QED trident spectrum. Using APEX test run data, we searched in the mass range 175-250 MeV, found no evidence for an A'→ e+ e- reaction, and set an upper limit of α'/α ~/= 10(-6).

Curaxins: anticancer compounds that simultaneously suppress NF-κB and activate p53 by targeting FACT.

Effective eradication of cancer requires treatment directed against multiple targets. The p53 and nuclear factor κB (NF-κB) pathways are dysregulated in nearly all tumors, making them attractive targets for therapeutic activation and inhibition, respectively. We have isolated and structurally optimized small molecules, curaxins, that simultaneously activate p53 and inhibit NF-κB without causing detectable genotoxicity.

New Measurement of the π0 radiative decay width.

High precision measurements of the differential cross sections for π0 photoproduction at forward angles for two nuclei, 12C and 208Pb, have been performed for incident photon energies of 4.9-5.5 GeV to extract the π0→γγ decay width.

Inhibition of encephalomyocarditis virus and poliovirus replication by quinacrine: implications for the design and discovery of novel antiviral drugs.

The 9-aminoacridine (9AA) derivative quinacrine (QC) has a long history of safe human use as an antiprotozoal and antirheumatic agent. QC intercalates into DNA and RNA and can inhibit DNA replication, RNA transcription, and protein synthesis. The extent of QC intercalation into RNA depends on the complexity of its secondary and tertiary structure.

Appearance of differentiation characteristics (induction of Ah-receptor-dependent genes) during cultivation of transformed cell clone K8 from embryonic rat fibroblasts.

The differentiation status of fibroblasts can be characterized by their ability to induce Ah-receptor-dependent genes. The ability to induce Ah-receptor-dependent genes encoding cytochrome P450 isoforms, Ah-receptor repressor, and NADPH-quinine oxidoreductase were studied in the transformed cell clone K8 obtained from immortalized embryonic rat fibroblasts by treatment with benzo(a)pyrene and in the parental clone F27. Treatment with benz(a)anthracene did not induce the genes in the transformed clone K8 on passages 4-14, but the induction was recorded in the transformed clone beginning from the 16th passage and later, whereas in F27 cells the induction was observed throughout the experiment.

Anti-malaria drug blocks proteotoxic stress response: anti-cancer implications.

The number of physical conditions and chemical agents induce accumulation of misfolded proteins creating proteotoxic stress. This leads to activation of adaptive pro-survival pathway, known as heat shock response (HSR), resulting in expression of additional chaperones. Several cancer treatment approaches, such as proteasome inhibitor Bortezomib and hsp90 inhibitor geldanamycin, involve activation of proteotoxic stress.

Measurement of direct f0(980) photoproduction on the proton.

We report on the results of the first measurement of exclusive f_{0}(980) meson photoproduction on protons for E_{gamma}=3.0-3.8 GeV and -t=0.

Targeting transcription factor NFkappaB: comparative analysis of proteasome and IKK inhibitors.

Nuclear factorkappaB (NFkappaB) plays a critical role in cancer development and progression. Thus, the NFkappaB signaling pathway provides important targets for cancer chemoprevention and anticancer chemotherapy. The central steps in NFkappaB activation are phosphorylation and proteasome-dependent degradation of its inhibitory proteins termed IkappaBs.

9-Aminoacridine-based anticancer drugs target the PI3K/AKT/mTOR, NF-kappaB and p53 pathways.

Acquisition of a transformed phenotype involves deregulation of several signal transduction pathways contributing to unconstrained cell growth. Understanding the interplay of different cancer-related signaling pathways is important for development of efficacious multitargeted anticancer drugs. The small molecule 9-aminoacridine (9AA) and its derivative, the antimalaria drug quinacrine, have selective toxicity for tumor cells and can simultaneously suppress nuclear factor-kappaB (NF-kappaB) and activate p53 signaling.

3He spin-dependent cross sections and sum rules.

We present a measurement of the spin-dependent cross sections for the 3He over -->(e over -->,e')X reaction in the quasielastic and resonance regions at a four-momentum transfer 0.1< or =Q2< or =0.9 GeV2.

Regulation of matrix metalloproteinase-9 transcription in squamous cell carcinoma of uterine cervix: the role of human papillomavirus gene E2 expression and activation of transcription factor NF-kappaB.

Matrix metalloproteinase-9 (MMP-9) plays an important role in initiation and progression of squamous cell carcinoma (SCC) of human uterine cervix. Regulation of MMP-9 expression in such tumors is insufficiently studied. Involvement of the human papillomavirus (HPV) gene E2 and transcription factor NF-kappaB in the regulation of MMP-9 transcription has been shown in some model systems and types of malignant tumors.

Quinacrine inhibits the epidermal dendritic cell migration initiating T cell-mediated skin inflammation.

Quinacrine (QC) is an anti-inflammatory drug that has been used for the treatment of malaria and rheumatoid diseases. The mechanism(s) underlying the anti-inflammatory activity of QC remains poorly understood. We recently reported the QC-mediated inhibition of the NF-kappaB pathway using an in vitro model.

Benzo[a]pyrene-dependent activation of transcription factors NF-kappaB and AP-1 related to tumor promotion in hepatoma cell cultures.

The activation by the carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) of transcription factors NF-kappaB and AP-1 in hepatoma 27 and HepG2 cell cultures was studied. In contrast to the hepatoma HepG2 cells, cytochrome P450 isoforms and Ah-receptor are not expressed in the hepatoma 27 cells. The transcription factor NF-kappaB was activated only in the hepatoma 27 cells by BP treatment but not by its noncarcinogenic isomer benzo[e]pyrene (BeP).