SUV39H1/H3K9me3 attenuates sulforaphane-induced apoptotic signaling in PC3 prostate cancer cells.

The isothiocyanate sulforaphane is a promising molecule for development as a therapeutic agent for patients with metastatic prostate cancer. Sulforaphane induces apoptosis in advanced prostate cancer cells, slows disease progression in vivo and is well tolerated at pharmacological doses. However, the underlying mechanism(s) responsible for cancer suppression remain to be fully elucidated. In this investigation we demonstrate that sulforaphane induces posttranslational modification of histone methyltransferase SUV39H1 in metastatic, androgen receptor-negative PC3 prostate cancer cells. Sulforaphane stimulates ubiquitination and acetylation of SUV39H1 within a C-terminal nuclear localization signal peptide motif and coincides with its dissociation from chromatin and a decrease in global trimethyl-histone H3 lysine 9 (H3K9me3) levels. Exogenous SUV39H1 expression leads to an increase in H3K9me3 and decreases sulforaphane-induced apoptotic signaling. SUV39H1 is thus identified as a novel mediator of sulforaphane cytotoxicity in PC3 cells. Our results also suggest SUV39H1 dynamics as a new therapeutic target in advanced prostate cancers.

The band structure of WO3 and non-rigid-band behaviour in Na0.67WO3 derived from soft x-ray spectroscopy and density functional theory.

The electronic structure of single-crystal WO3 and Na0.67WO3 (a sodium-tungsten bronze) has been measured using soft x-ray absorption and resonant soft x-ray emission oxygen K-edge spectroscopies. The spectral features show clear differences in energy and intensity between WO3 and Na0.67WO3. The x-ray emission spectrum of metallic Na0.67WO3 terminates in a distinct Fermi edge. The rigid-band model fails to explain the electronic structure of Na0.67WO3 in terms of a simple addition of electrons to the conduction band of WO3. Instead, Na bonding and Na 3s-O 2p hybridization need to be considered for the sodium-tungsten bronze, along with occupation of the bottom of the conduction band. Furthermore, the anisotropy in the band structure of monoclinic γ-WO3 revealed by the experimental spectra with orbital-resolved geometry is explained via density functional theory calculations. For γ-WO3 itself, good agreement is found between the experimental O K-edge spectra and the theoretical partial density of states of O 2p orbitals. Indirect and direct bandgaps of insulating WO3 are determined from extrapolating separations between spectral leading edges and accounting for the core-hole energy shift in the absorption process. The O 2p non-bonding states show upward band dispersion as a function of incident photon energy for both compounds, which is explained using the calculated band structure and experimental geometry.

First Report of Transmission of Little cherry virus 2 to Sweet Cherry by Pseudococcus maritimus (Ehrhorn) (Hemiptera: Pseudococcidae).

Little cherry virus 2 (LChV2; genus Ampelovirus, family Closteroviridae) is associated with Little Cherry Disease (LCD), one of the most economically destructive diseases of sweet cherry (Prunus avium (L.)) in North America (1). Since 2010, incidence of LCD associated with LChV2 confirmed by reverse transcription (RT)-PCR assays has increased in orchards of Washington State. LChV2 was known to be transmitted by the apple mealybug (Phenacoccus aceris (Signoret)) (3). However, the introduction of Allotropus utilis, a parasitoid platygastrid wasp (2) for biological control, contributed to keeping insect populations below the economic threshhold. In recent years, the population of grape mealybug (Pseudococcus maritimus (Ehrhorn)) increased in cherry orchards of Washington State (Beers, personal observation). Since grape mealybug is reported to transmit Grapevine leafroll associated virus 3 (Ampelovirus) in grapevine (4), this study investigated whether this insect would also transmit LChV2. A colony of grape mealybugs on Myrobalan plum (Prunus cerasifera Ehrh.) trees was identified visually and morphologically from slide mounts. In a growth chamber, first and second instar crawlers were fed on fresh cut shoots of sweet cherry infected with a North American strain (LC5) of LChV2. After an acquisition period of 7 days, 50 crawlers were transferred to each young potted sweet cherry trees, cv. Bing, confirmed free from LChV2 by RT-PCR. This process was repeated in two trials to yield a total of 21 potted trees exposed to grape mealybug. One additional tree was left uninfested as a negative control. After 1 week, the trees were treated with pesticide to eliminate the mealybugs. Two to four months after the inoculation period, leaves were collected from each of the recipient trees and tested by RT-PCR for the presence of LChV2. To reduce the possibility of virus contamination from residual mealybug debris on leaf surfaces, the trees were allowed to defoliate naturally. After a 3-month dormant period, the new foliage that emerged was then tested. Two sets of primers: LC26L (GCAGTACGTTCGATAAGAG) and LC26R (AACCACTTGATAGTGTCCT) (1); and LC2.13007F (GTTCGAAAGTGTTTCTTGA) and LC2.14545R (CATTATYTTACTAATGGTATGAC) (this study) were used to amplify a partial segment of the replicase gene (409 bp) and the complete (1,080 bp) coat protein gene of LChV2, respectively. Of 21 trees tested, 18 yielded positive results for LChV2. The reaction products from six randomly selected trees were cloned and the virus identity was verified by sequencing. The sequences of RT-PCR amplicons from both primer pairs showed ≥99% identity to LChV2, strain LC5 (GenBank Accession No. AF416335). The result confirmed that P. maritimus transmits LChV2, a significant finding for this cherry production region. Grape mealybug is of increasing concern in the tree fruit industry because it is difficult to control in established orchards. The presence of infested orchards that serve as reservoirs of both LCD and this insect vector present a challenge for management. To the best of our knowledge this is the first report to show transmission of LChV2 by grape mealybug. References: (1) K. C. Eastwell and M. G. Bernardy. Phytopathology 91:268, 2001. (2) C. F. W. Muesbeck. Can Entomol. 71:158, 1939. (3) J. R. D. Raine et al. Can. J. Plant Pathol. 8:6, 1986. (4) R. Sforza et al. Eur. J. Plant Pathol. 109:975, 2003.

Chemical bonding in copper-based transparent conducting oxides: CuMO2 (M = In, Ga, Sc).

The geometry and electronic structure of copper-based p-type delafossite transparent conducting oxides, CuMO(2) (M = In, Ga, Sc), are studied using the generalized gradient approximation (GGA) corrected for on-site Coulomb interactions (GGA + U). The bonding and valence band compositions of these materials are investigated, and the origins of changes in the valence band features between group 3 and group 13 cations are discussed. Analysis of the effective masses at the valence and conduction band edge explains the experimentally reported conductivity trends.

High levels of exotic armored scales on imported avocados raise concerns regarding USDA-APHIS' phytosanitary risk assessment.

Between 1914 and 2007, a quarantine protected California avocado, Persea americana Mill., groves from pests that might be introduced into the state along with fresh, imported avocados. Soon after Mexican avocados were first allowed entry on 1 February 2007, live specimens of several species of armored scales (Hemiptera: Diaspididae) not believed to be present in California were detected on 'Hass' avocados entering the state from Mexico. Initially, the California Department of Food and Agriculture (CDFA) prevented avocados infested with these scales from entering the state or required that they be fumigated with an approved treatment such as methyl bromide. After a Science Advisory Panel meeting in May 2007, U.S. Department of Agriculture-Animal and Plant Health Inspection Service (USDA-APHIS) reaffirmed its position that armored scales on shipments of fruit for consumption (including avocados) pose a "low risk" for pest establishment. In compliance with APHIS protocols, as of 18 July 2007, CDFA altered its policy to allow shipments of scale-infested avocados into the state without treatment. Here, we report on sampling Mexican avocados over an 8-mo period, September 2007-April 2008. An estimated 67 million Mexican Hass avocados entered California over this period. Based on samples from 140 trucks containing approximately 15.6% of this volume of fruit, we estimate that approximately 47.6 million live, sessile armored scales and an additional 20.1 million live eggs and crawlers were imported. We found eight probable species of armored scales in the samples, seven of these are not believed to occur in California; 89.3% of the live scales were Abgrallaspis aguacatae Evans, Watson and Miller, a recently described species. In contrast to the USDA-APHIS opinion, we believe the volume of shipments and levels of live scales they contain present a significant risk to California's US$300 million avocado industry and to other crops that might become infested by one or more of these exotic species.

Intrinsic ferromagnetism in CeO(2): dispelling the myth of vacancy site localization mediated superexchange.

Intrinsic ferromagnetism in CeO(2) is a source of controversy in the literature and has been linked to the excess electrons left over upon oxygen vacancy formation on Ce sites neighbouring the vacancy. A recent theoretical study (Han et al 2009 Phys. Rev. B 79 100403) concluded that increased vacancy concentration changes the localization behaviour of CeO(2), resulting in some degree of charge localization in the vacancy site itself, which leads to superexchange and polarization effects that enhance the stability of ferromagnetism. In this report, we show conclusively that oxygen vacancy concentrations of up to 12.5% do not cause localization in the vacancy site, and that this is not responsible for any enhanced ferromagnetism. Investigation of oxygen vacancies on the (111), (110) and (100) low index surfaces also show no evidence for ferromagnetic preference.

Electronic origins of structural distortions in post-transition metal oxides: experimental and theoretical evidence for a revision of the lone pair model.

Structural distortions in post-transition metal oxides are often explained in terms of the influence of sp hybrid "lone pairs." Evidence is presented here showing that this model must be revised. The electronic structures of prototypically distorted alpha-PbO and alpha-Bi2O3 have been measured by high-resolution x-ray photoemission and soft x-ray emission spectroscopies. In contrast with the expectations of the lone pair model, a high density of metal 6s states is observed at the bottom of the valence band. The measurements are consistent with the results of density functional theory calculations.

Caries incidence following restoration of shortened lower dental arches in a randomized controlled trial.

CONTEXT: Removable partial dentures used to restore the shortened lower dental arch may adversely affect the remaining natural teeth and are associated with a low prevalence of use. OBJECTIVE: To report the findings for caries incidence 2 years after restoration of lower shortened arches with bilateral cantilever resin-bonded bridges (RBBs) and conventional partial dentures (RPDs). DESIGN: Randomised controlled trial. SETTING: Secondary care PATIENTS: 25 male and 35 female subjects of median age 67 years. were randomly allocated to 'bridge' and 'denture' treatment groups of 30 patients each matched for age and sex. Caries incidence was recorded during dental examinations 3 months, 1 and 2 years after insertion of new lower prostheses. INTERVENTIONS: Cantilever RBBs and conventional RPDs with cast metal frameworks. RESULTS: There was a highly significant difference in the frequency of new caries lesions, 11 and 51 in the bridge and denture groups respectively (P < 0.01). 20 out of 27 bridge patients and 9 of 23 denture patients had no caries experience. Multivariate modeling identified treatment group as the only significant predictor of caries occurrence. CONCLUSIONS: Two years after restoration of lower shortened arches for an elderly sample of patients, there was a significantly greater incidence of new and recurrent caries lesions in subjects restored with RPDs compared with cantilever RBBs.

Flumazenil: an unreliable antagonist in baclofen overdose.

We report a case of inadvertent overdose of baclofen given intrathecally resulting in coma. This was unresponsive to flumazenil and required supportive intensive therapy. With the increasing use of baclofen intrathecally for spasticity and its wide interpatient dose variability, there is a need to find a safe antagonist to baclofen for routine medical use.

Listeria cerebritis: relapse of infection in renal transplant patients.

In 3 cases of Listeria cerebritis, two of the patients had relapse with cerebritis after antimicrobial therapy for acute Listeria septicemia or meningitis. Each had received ten to 14 days of intravenous penicillin. Relapse occurred with fever and sudden focal cerebral dysfunction. Brain scans showed focal uptake; arteriograms and computerized tomography were normal. Cerebrospinal fluids were nondiagnostic; blood cultures yielded Listeria in two patients. Penicillin treatment for six weeks produced rapid clinical responses that were complete in one and minimal residual in two. Progress brain scans were normal. A relapse rate of 35% is reported in transplant patients with Listeria meningitis and/or bacteremia who are treated for less than three weeks; to our knowledge, cerebritis in such patients has not been reported previously. High-dose penicillin or ampicillin therapy for four to six weeks is recommended for Listeria infections in this select group.

Ten-year survival rates in breast cancer using combination chemotherapy.

The outcome in 254 patients with all stages of breast cancer treated by combination chemotherapy is presented. All the patients were treated 10 or more years ago. The 10-year survival rate for Stages I and II combined is 60 per cent, in Stage III 19 per cent and in Stage IV 3 per cent. The combined rate in Stages I and II differed markedly according to hormonal status. In premenopausal patients the rate was 84 per cent compared with 42 per cent in postmenopausal patients.