PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.

BackgroundMaintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.MethodsWe developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC.ResultsThe level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre.ConclusionsPR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model

Efficacy of pegylated interferon α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy

BACKGROUND: Improving the HBe seroconversion rate of patients without HBeAg loss after long-term lamivudine therapy has become an urgent clinical problem that we have to face. Unfortunately, there is no consensus on the mananement of these patients. The aim of this study was to evaluate the efficacy of pegylated interferon (PEG-IFN) α2a in patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. METHODS: Fifty patients with chronic hepatitis B without the loss of HBeAg after ≥96 weeks of lamivudine treatment were enrolled to withdraw from treatment to induce a biochemical breakthrough. Patients who achieved a biochemical breakthrough within 24 weeks received 48-weeks of PEG-IFN α2a therapy, and were then assessed during a subsequent 24-week follow-up period. RESULTS: Forty-three (86.0%) patients achieved a biochemical breakthrough within 24 weeks of lamivudine withdrawal. The rates of combined response (both undetectable HBV DNA and HBeAg loss) and HBsAg loss were alone 51.2% and 20.9%, respectively after 48 weeks of PEG-IFN α2a therapy, and 44.2% and 18.6%, respectively, at 24 weeks after treatment cessation. The end-of-treatment combined response rate was 65.4% among patients with a baseline HBsAg <20,000 IU/mL, which was significantly higher than 29.4% of patients with HBsAg ≥20,000 IU/mL (P=0.031). For patients with HBsAg levels <1,500 IU/mL at 12 and 24 weeks therapy, the end-of-treatment combined response rate was 68.2% and 69.0%, which were both significantly higher than patients with HBsAg ≥1,500 IU/mL (33.3% and 14.3%; P=0.048 and 0.001). The end-of-treatment combined response rate was significantly higher among patients with HBV DNA<10(5) copies/mL (76.2%) compared to patients with HBV DNA ≥10(5) copies/mL (27.3%) after 24 weeks of therapy (P=0.004). CONCLUSION: Retreatment with PEG-IFN α2a was effective and safe for patients without HBeAg loss after the withdrawal of long-term lamivudine therapy. HBsAg levels at the baseline, 12 and 24 weeks of therapy, and HBV DNA levels at 24 weeks of therapy, can predict the effect of PEG-IFN α2a after 48 weeks of therapy

A multichannel thiacalix[4]arene-based fluorescent chemosensor for Zn²⁺, F⁻ ions and imaging of living cells

The fluorescent sensor (3) based on the 1,3-alternate conformation of the thiacalix[4]arene bearing the coumarin fluorophore, appended via an imino group, has been synthesised. Sensing properties were evaluated in terms of a colorimetric and fluorescence sensor for Zn 2+ and F - . High selectivity and excellent sensitivity were exhibited, and off-on optical behaviour in different media was observed. All changes were visible to the naked eye, whilst the presence of the Zn 2+ and F - induces fluorescence enhancement and the formation of a 1:1 complex with 3. In addition, 3 exhibits low cytotoxicity and good cell permeability and can readily be employed for assessing the change of intracellular levels of Zn 2+ and F -

FCS-MPC upravljačka strategija novim trorazinskim izmjenjivačem otpornim na kvarove

In order to meet the high reliability of aviation inverters, the paper established a new three-level inverter which can increase the reliability in safety-critical applications, what\u27s more, the new topology adding assistant leg to control neutral-point voltage independently. On the basis of the new topology, a mixed logic dynamic (MLD) model was established for the new inverter circuits, and takes finite control set model predictive control (FCS-MPC) for the new inverter. The method takes a discrete-time model of inverter to predict the future value of the all possible voltage vectors generated by the inverter. The vector which minimizes objective function in finite control set is selected as the control of inverter, the objective function used in this work evaluates the voltage error and the switch frequency at the next sampling time. The paper explicitly researched the solving algorithm and realization procedure of the new inverter circuit, its feasibility and validity is verified by the experiment.Za postizanje visokog stupnja pouzdanosti avijacijskih izmjenjivača, u radu je postavljena nova topologija trorazinskog izmjenjivača za primjene u sigurnosno kritičnim sustavima koja ima dodatnu pomoćnu granu za nezavisno upravljanje naponom neutralne točke. Zasnivajući se na ovoj novoj topologiji, dinamički model s mješovitom logikom (MLD) postavljen je za električne krugove novog ispravljača koji za upravljanje pretvaračem koriste konačni skup upravljačkih signala dobivenih modelskog prediktivnog upravljanja (FCS-MPC). Metoda koristi vremenski diskretni model izmjenjivača za predviđanje budućih vrijednosti svih mogućih vektora napona koje generira izmjenjivač. Za upravljanje pretvaračem koristi se upravljački vektor iz konačnog skupa upravljačkih signala dobiven minimiziranjem funkcije cilja koja u obzir uzima grešku napona i frekvenciju sklapanja u sljedećem koraku diskretizacije. U radu je izravno razvijen algoritam za rješavanje problema i procedura za realizaciju nove topologije izmjenjivača, a izvedivost i validnost provjereni su eksperimentalno

(E)-Ethyl N′-[1-(4-methoxy­phen­yl)ethyl­idene]hydrazinecarboxyl­ate

The mol­ecule of the title compound, C12H16N2O3, adopts a trans configuration with respect to the C=N bond. The dihedral angle between the benzene ring and the hydrazinecarboxyl­ate plane is 13.82 (6)°. In the crystal structure, mol­ecules are linked into centrosymmetric dimers by N—H⋯O and C—H⋯O hydrogen bonds, and the dimers are linked together by C—H⋯π inter­actions

O R I G I N A L A R T I C L E Effects of dietary corn oil and vitamin E supplementation on fatty acid profiles and expression of acetyl CoA carboxylase and stearoyl-CoA desaturase gene in Hu sheepa sj_731 165..171

ABSTRACT This study was conducted to assess the effects of dietary corn oil and vitamin E supplementation on fatty acid (FA) profiles and abundances of acetyl-CoA carboxylase (ACC) and D 9 stearoyl-CoA desaturase (SCD) mRNA of Hu sheep. Animals were allocated to three dietary treatments: basal and supplemented with 3% corn oil (CNO), or CNO plus 500 mg/kg vitamin E (COE). The experiment lasted for 10 weeks. No differences were observed in growth performance and carcass qualities among the three treatments (P &gt; 0.05). Feeding CNO and COE diets increased polyunsaturated FAs including cis 9 trans 11 conjugated linoleic acid, and decreased saturated FA in longissimus muscle (P &lt; 0.05). The mRNA abundances of ACC and SCD as detected by real-time PCR were reduced (P &lt; 0.05) in liver and subcutaneous fat by supplementary oil, while the SCD mRNA level in longissimus muscle was also reduced (P &lt; 0.05). Inclusion of vitamin E did not have further effects on mRNA abundances of these two enzymes. It is suggested that dietary corn oil supplementation may reduce FA biosynthesis and influence FA profiles in Hu sheep through decreased expression of both ACC and SCD genes