siRNA-induced immunostimulation through TLR7 promotes antitumoral activity against HPV-driven tumors in vivo

Oncogene-specific downregulation mediated by RNA interference (RNAi) is a promising avenue for cancer therapy. In addition to specific gene silencing, in vivo RNAi treatment with short interfering RNAs (siRNAs) can initiate immune activation through innate immune receptors including Toll-like receptors, (TLRs) 7 and 8. Two recent studies have shown that activation of innate immunity by addition of tri-phosphate motifs to oncogene-specific siRNAs, or by co-treatment with CpG oligos, can potentiate siRNA antitumor effects. To date, there are no reports on applying such approach against human papillomavirus (HPV)-driven cancers. Here, we characterized the antitumor effects of non-modified siRNAs that can target a specific oncogene and/or recruit the innate immune system against HPV-driven tumors. Following the characterization of silencing efficacy and TLR7 immunostimulatory potential of 15 siRNAs targeting the HPV type 16 E6/E7 oncogenes, we identified a bifunctional siRNA sequence that displayed both potent gene silencing and active immunostimulation effect. In vivo systemic administration of this siRNA resulted in reduced growth of established TC-1 tumors in C57BL/6 mice. Ablation of TLR7 recruitment via 2′O-methyl modification of the oligo backbone reduced these antitumor effects. Further, a highly immunostimulatory, but non-HPV targeting siRNA was also able to exert antitumoral effects although for less prolonged time compared with the bifunctional siRNA. Collectively, our work demonstrates for the first time that siRNA-induced immunostimulation can have antitumoral effects against HPV-driven tumors in vivo, even independent of gene silencing efficacy

Entanglement and Timing-Based Mechanisms in the Coherent Control of Scattering Processes

The coherent control of scattering processes is considered, with electron impact dissociation of H$_2^+$ used as an example. The physical mechanism underlying coherently controlled stationary state scattering is exposed by analyzing a control scenario that relies on previously established entanglement requirements between the scattering partners. Specifically, initial state entanglement assures that all collisions in the scattering volume yield the desirable scattering configuration. Scattering is controlled by preparing the particular internal state wave function that leads to the favored collisional configuration in the collision volume. This insight allows coherent control to be extended to the case of time-dependent scattering. Specifically, we identify reactive scattering scenarios using incident wave packets of translational motion where coherent control is operational and initial state entanglement is unnecessary. Both the stationary and time-dependent scenarios incorporate extended coherence features, making them physically distinct. From a theoretical point of view, this work represents a large step forward in the qualitative understanding of coherently controlled reactive scattering. From an experimental viewpoint, it offers an alternative to entanglement-based control schemes. However, both methods present significant challenges to existing experimental technologies

The effect of cigarette smoking during Pregnancy on endocrine Pancreatic Function and Fetal growth: a Pilot study

Introduction: Cigarette smoking in pregnancy is a common cause of fetal growth restriction. We aimed to investigate endocrine pancreatic function of motherinfant dyads in relation to cigarette smoking, as a possible mechanism for the poor fetal growth. Methods: Prospective study of smoking mothers (10 cigarettes or more per day, self-reported to the midwife) and non-smoker control mothers during their first pregnancy. Insulin, glucose, C-peptide, HbA1C, fructosamine, prolactin, serotonin, and cortisol were measured in maternal blood at 2426 weeks and in umbilical cord blood at birth. Cotinine was also measured in cord blood. Results: Of 37 smokers and 36 non-smokers recruited, cord blood was obtainable from 38 babies (19 in each group). In utero cigarette exposure was associated with lower birthweight (3,035 +/- 490 versus 3,405 +/- 598 g, p = 0.005), with linear modeling of the smoking cohort showing a 41 g reduction for every increase of one cigarette smoked per day (95% CI -71 to -11 g, p = 0.010). There were no differences between groups in indices of maternal or perinatal endocrine pancreatic dysfunction. Heavier smoking independently correlated with higher maternal fasting levels of glucose (p = 0.044) and C-peptide (p = 0.011). We did not observe any significant associations between the daily number of cigarettes and any of the cord blood parameters. We also looked for differences between cohorts based on infant gender. Serotonin levels were higher in smoking mothers with male fetuses (p = 0.01 to p = 0.004). Conclusion: Endocrine pancreatic dysfunction does not appear to be a major contributing factor to nicotine-associated fetal growth restriction. The higher serotonin levels in smoking mothers carrying male infants is of uncertain significance but could be a manifestation of gender differences in susceptibility to the long-term effects of cigarette smoking.This study was supported by the Nepean Medical Research Foundation

Thermal Instability in Gravitationally-Stratified Plasmas: Implications for Multi-Phase Structure in Clusters and Galaxy Halos

We study the interplay among cooling, heating, conduction, and magnetic fields in gravitationally stratified plasmas using simplified, plane-parallel numerical simulations. Since the physical heating mechanism remains uncertain in massive halos such as groups or clusters, we adopt a simple, observationally-motivated prescription which enforces global thermal equilibrium when averaged over large scales. The plasma remains susceptible to local thermal instability, however, and cooling drives an inward flow of material. In contrast to previous results, we argue that the thermal stability of the plasma is independent of its convective stability. We find that the ratio of the cooling timescale to the dynamical timescale t_cool/t_ff controls the saturation of the thermal instability: when t_cool/t_ff < 1, the plasma develops extended multi-phase structure, whereas when t_cool / t_ff > 1 it does not. (In a companion paper, we show that the criterion for thermal instability in a spherical potential is somewhat less stringent, t_cool / t_ff < 10.) When thermal conduction is anisotropic with respect to the magnetic field, the criterion for multi-phase structure is essentially independent of the thermal conductivity of the plasma. Our criterion for local thermal instability to produce multi-phase structure is an extension of the cold vs. hot accretion modes in galaxy formation that applies at all radii in hot halos, not just to the virial shock. We show that this criterion is consistent with data on multi-phase gas in the ACCEPT sample of clusters; in addition, when t_cool / t_ff > 1, the net cooling rate to low temperatures and the mass flux to small radii are suppressed enough relative to models without heating to be qualitatively consistent with star formation rates and x-ray line emission in groups and clusters.Comment: This is an electronic version of an article published in Monthly Notices of the Royal Astronomical Society, Volume 419, Issue 4, pp. 3319-333

Maternal super-obesity and perinatal outcomes in Australia: A national population-based cohort study

© 2015 Sullivan et al. Background: Super-obesity is associated with significantly elevated rates of obstetric complications, adverse perinatal outcomes and interventions. The purpose of this study was to determine the prevalence, risk factors, management and perinatal outcomes of super-obese women giving birth in Australia. Methods: A national population-based cohort study. Super-obese pregnant women (body mass index (BMI) >50 kg/m2 or weight >140 kg) who gave birth between January 1 and October 31, 2010 and a comparison cohort were identified using the Australasian Maternity Outcomes Surveillance System (AMOSS). Outcomes included maternal and perinatal morbidity and mortality. Prevalence estimates calculated with 95 % confidence intervals (CIs). Adjusted odds ratios (ORs) were calculated using multivariable logistic regression. Results: 370 super-obese women with a median BMI of 52.8 kg/m2 (range 40.9-79.9 kg/m2) and prevalence of 2.1 per 1 000 women giving birth (95 % CI: 1.96-2.40). Super-obese women were significantly more likely to be public patients (96.2 %), smoke (23.8 %) and be socio-economically disadvantaged (36.2 %). Compared with other women, super-obese women had a significantly higher risk for obstetric (adjusted odds ratio (AOR) 2.42, 95 % CI: 1.77-3.29) and medical (AOR: 2.89, 95 % CI: 2.64-4.11) complications during pregnancy, birth by caesarean section (51.6 %) and admission to special care (HDU/ICU) (6.2 %). The 372 babies born to 365 super-obese women with outcomes known had significantly higher rates of birthweight ≥4500 g (AOR 19.94, 95 % CI: 6.81-58.36), hospital transfer (AOR 3.81, 95 % CI: 1.93-7.55) and admission to Neonatal Intensive Care Unit (NICU) (AOR 1.83, 95 % CI: 1.27-2.65) compared to babies of the comparison group, but not prematurity (10.5 % versus 9.2 %) or perinatal mortality (11.0 (95 % CI: 4.3-28.0) versus 6.6 (95 % CI: 2.6- 16.8) per 1 000 singleton births). Conclusions: Super-obesity in pregnancy in Australia is associated with increased rates of pregnancy and birth complications, and with social disadvantage. There is an urgent need to further address risk factors leading to super-obesity among pregnant women and for maternity services to better address pre-pregnancy and pregnancy care to reduce associated inequalities in perinatal outcomes

Helicobacter pylori (H pylori) infection in Greece: the changing prevalence during a ten-year period and its antigenic profile

BACKGROUND: To evaluate changes in H pylori infection prevalence in Greece during a ten-year period, and to examine its antigenic profile. METHODS: Three groups of patients were studied. Group O-87: Banked serum samples of 200 consecutive adult outpatients, from the Hepato-Gastroenterology clinic of a teaching hospital at Athens, collected in 1987. Group O-97: Serum samples of 201 similarly selected outpatients from the same Unit, collected in 1997. Group BD-97: Serum samples of 120 consecutive blood donors from the same hospital, collected in 1997. H pylori IgG antibody seroprevalence was studied by a quantitative ELISA. Antigenic profile was studied by western-blot IgG assay, in 62 IgG positive patients of O-97 and BD-97. Results were analyzed by conventional statistics and multivariate regression analysis. RESULTS: The H pylori seroprevalence increased with age in the three tested groups. In O-97, seroprevalence did not differ from that, in BD-97. On the contrary, there was a significant decrease in seropositivity between O-87 and O-97 (59.5% vs 49.2%, p = 0.039). Multiple regression analysis showed that age over 35 years (OR:3.45, 95% CI:1.59–7.49, p = 0.002) and year of patients' selection – that is 1987 or 1997 – (OR:1.73, 95% CI:1.14–2.65 for 1987, p = 0.010), were independent risk factors of H pylori infection. The seroprevalence of CagA+ and VacA+ strains was 77.4% and 58.5%, respectively, and type I(CagA+/VacA+) strains were significantly more common than type II(CagA-/VacA-) strains (59.7% vs 22.6%, p < 0.001). CONCLUSIONS: During a ten-year period, we found a significant decrease of H pylori infection in Greece and our data support the birth cohort phenomenon as an explanation for the age-dependent increase of H pylori infection. The prevalence of CagA and/or VacA positive strains is relatively high, in a country with low incidence of gastric cancer

Calibration of Ultraviolet, Mid-infrared, and Radio Star Formation Rate Indicators

We present calibrations for star formation rate (SFR) indicators in the ultraviolet, mid-infrared, and radio-continuum bands, including one of the first direct calibrations of 150 MHz as an SFR indicator. Our calibrations utilize 66 nearby star-forming galaxies with Balmer-decrement-corrected luminosities, which span five orders of magnitude in SFR and have absolute magnitudes of -24 < M_r < -12. Most of our photometry and spectrophotometry are measured from the same region of each galaxy, and our spectrophotometry has been validated with SDSS photometry, so our random and systematic errors are small relative to the intrinsic scatter seen in SFR indicator calibrations. We find that the Wide-field Infrared Space Explorer W4 (22.8 μm), Spitzer 24 μm, and 1.4 GHz bands have tight correlations with the Balmer-decrement-corrected Hα luminosity, with a scatter of only 0.2 dex. Our calibrations are comparable to those from the prior literature for L* galaxies, but for dwarf galaxies, our calibrations can give SFRs that are far greater than those derived from most previous literature

Crop updates 2006 - Farming Systems

This session covers nineteen papers from different authors: SOIL AND NUTRIENT MANAGEMENT 1. Inve$tigating fertili$er inve$tment, Wayne Pluske, Nutrient Management Systems 2. KASM, the potassium in Agricultural System Model,Bill Bowden and Craig Scanlan, DAWA Northam and UWA, School of Earth and Geographical Sciences 3. Long term productivity and economic benefits of subsurface acidity management from surface and subsurface liming, Stephen Davies, Chris Gazey and Peter Tozer, Department of Agriculture 4. Furrow and ridges to prevent waterlogging, Dr Derk Bakker, Department of Agriculture 5. Nitrous oxide emissions from a cropped soil in Western Australia, Louise Barton1, David Gatter2, Renee Buck1, Daniel Murphy1, Christoph Hinz1and Bill Porter2 1School of Earth and Geographical Sciences, The University of Western Australia, 2Department of Agriculture GROWER DECISIONS 6. Managing the unmanageable, Bill Bowden Department of Agriculture 7. Review of climate model summaries reported in Department of Agriculture’s Season Outlook, Meredith Fairbanks, Department of Agriculture 8. Mapping the frost risk in Western Australia, Nicolyn Short and Ian Foster, Department of Agriculture 9. .35 kg/ha.day and other myths, James Fisher, Doug Abrecht and Mario D’Antuono, Department of Agriculture 10. Gaining with growers – Lessons from a successful alliance of WA Grower Groups, Tracey M. Gianatti, Grower Group Alliance 11. WA Agribusiness Trial Network Roundup – 2005, Paul Carmody, Local Farmer Group Network, UWA 12. Drivers of no-till adoption, Frank D’Emdenabc, Rick Llewellynabdand Michael Burtonb,aCRC Australian Weed Management; bSchool of Agricultural and Resource Economics, UWA. cDepartment of Agriculture, dCSIRO Sustainable Ecosystems, Adelaide PRODUCTION SYSTEMS, PRECISION AGRICULTURE AND SUSTAINABILITY 13. Maintaining wheat and lupin yields using phase pastures and shielded sprayers to manage increasing herbicide resistance, Caroline Peek, Nadine Eva, Chris Carter and Megan Abrahams, Department of Agriculture 14. Analaysis of a wheat-pasture rotation in the 330mm annual rainfall zone using the STEP model, Andrew Blake and Caroline Peek, Department of Agriculture 15. Response to winter drought by wheat on shallow soil with low seeding rate and wide row spacing, Paul Blackwell1, Sylvain Pottier2and Bill Bowden1 1 Department of Agriculture; 2Esitpa (France) 16. How much yield variation do you need to justify zoning inputs? Michael Robertson and Greg Lyle, CSIRO Floreat, Bill Bowden, Department of Agriculture; Lisa Brennan, CSIRO Brisbane 17. Automatic guidance and wheat row position: On-row versus between-row seeding at various rates of banded P fertilisers, Tony J. Vyn1, Simon Teakle2, Peter Norris3and Paul Blackwell4,1Purdue University, USA; 2Landmark; 3Agronomy for Profit; 4 Department of Agriculture 18. Assessing the sustainability of high production systems (Avon Agricultural Systems Project), Jeff Russell and James Fisher, Department of Agriculture, Roy Murray-Prior and Deb Pritchard, Muresk Institute; Mike Collins, ex WANTFA, 19. The application of precision agriculture techniques to assess the effectiveness of raised beds on saline land in WA, Derk Bakker, Greg Hamilton, Rob Hetherington, Andrew Van Burgel and Cliff Spann, Department of Agricultur

MUC1 Limits Helicobacter pylori Infection both by Steric Hindrance and by Acting as a Releasable Decoy

The bacterium Helicobacter pylori can cause peptic ulcer disease, gastric adenocarcinoma and MALT lymphoma. The cell-surface mucin MUC1 is a large glycoprotein which is highly expressed on the mucosal surface and limits the density of H. pylori in a murine infection model. We now demonstrate that by using the BabA and SabA adhesins, H. pylori bind MUC1 isolated from human gastric cells and MUC1 shed into gastric juice. Both H. pylori carrying these adhesins, and beads coated with MUC1 antibodies, induced shedding of MUC1 from MKN7 human gastric epithelial cells, and shed MUC1 was found bound to H. pylori. Shedding of MUC1 from non-infected cells was not mediated by the known MUC1 sheddases ADAM17 and MMP-14. However, knockdown of MMP-14 partially affected MUC1 release early in infection, whereas ADAM17 had no effect. Thus, it is likely that shedding is mediated both by proteases and by disassociation of the non-covalent interaction between the α- and β-subunits. H. pylori bound more readily to MUC1 depleted cells even when the bacteria lacked the BabA and SabA adhesins, showing that MUC1 inhibits attachment even when bacteria cannot bind to the mucin. Bacteria lacking both the BabA and SabA adhesins caused less apoptosis in MKN7 cells than wild-type bacteria, having a greater effect than deletion of the CagA pathogenicity gene. Deficiency of MUC1/Muc1 resulted in increased epithelial cell apoptosis, both in MKN7 cells in vitro, and in H. pylori infected mice. Thus, MUC1 protects the epithelium from non-MUC1 binding bacteria by inhibiting adhesion to the cell surface by steric hindrance, and from MUC1-binding bacteria by acting as a releasable decoy