Relationships between the multiplication of chronic bee-paralysis virus and its associate particle

The amounts of chronic bee-paralysis virus associate (CPVA) produced in bees injected with purified chronic bee-paralysis virus (CPV) were negatively associated with the amounts, lengths of particles and maximum sedimentation coefficients of CPV. The ratio of the amounts of CPV/CPVA varied widely between individuals, but more CPVA was produced and CPV/CPVA ratios were smaller when CPVA was injected with the CPV preparations than when the latter were injected alone. The multiplication of the RNAs of CPV and of CPVA were also negatively correlated. The nature of the relationship between CPV and CPVA and the packaging arrangement of CPV RNA are discussed

Self-Organizing Maps Algorithm for Parton Distribution Functions Extraction

We describe a new method to extract parton distribution functions from hard scattering processes based on Self-Organizing Maps. The extension to a larger, and more complex class of soft matrix elements, including generalized parton distributions is also discussed.Comment: 6 pages, 3 figures, to be published in the proceedings of ACAT 2011, 14th International Workshop on Advanced Computing and Analysis Techniques in Physics Researc

Untangling the ATR-CHEK1 network for prognostication, prediction and therapeutic target validation in breast cancer

Background: ATR-Chk1 signalling network is critical for genomic stability. ATR-Chk1 may be deregulated in breast cancer and have prognostic, predictive and therapeutic significance. Patients and methods: We investigated ATR and phosphorylated CHK1Ser345 protein (pChk1) expression in 1712 breast cancers (Nottingham Tenovus series). ATR and Chk1 mRNA were evaluated in 1950 breast cancers (METABRIC cohort). Pre-clinically, biological consequences of ATR gene knockdown or ATR inhibition by small molecule inhibitor (VE-821) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines and in non-tumorigenic breast epithelial cells (MCF10A). Results: High ATR and high cytoplasmic pChk1 expression was significantly associated with higher tumour stage, higher mitotic index, pleomorphism and lymphovascular invasion. In univariate analysis, high ATR and high cytoplasmic pChk1 protein expression was associated with shorter breast cancer specific survival (BCSS). In multivariate analysis, high ATR remains an independent predictor of adverse outcome. At the mRNA level, high Chk1 remains associated with aggressive phenotypes including lymph node positivity, high grade, Her-2 overexpression, triple-negative phenotype and molecular classes associated with aggressive behaviour and shorter survival.. Pre-clinically, Chk1 phosphorylation at serine 345 following replication stress (induced by gemcitabine or hydroxyurea treatment) was impaired in ATR knockdown and in VE-821 treated breast cancer cells. Doxycycline inducible knockdown of ATR suppressed growth, which was restored when ATR was re-expressed. Similarly, VE-821 treatment resulted in a dose dependent suppression of cancer cell growth and survival (MCF7 and MDA-MB-231) but had no effect on non-tumorigenic breast epithelial cells (MCF10A). Conclusions: We provides evidence that ATR and Chk1 are promising biomarkers and rational drug target for personalized therapy in breast cancer

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy

BRCA1, a key factor in homologous recombination repair may also regulate base excision repair (BER). Targeting BRCA1-BER deficient cells by blockade of ATM and DNA-PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n=1602 sporadic and n=50 germ-line BRCA1 mutated) and mRNA expression in two cohorts (n=1952 and n=249). Artificial neural network analysis for BRCA1-DNA repair interacting genes was conducted in 249 tumours. Pre-clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA-PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p<0.0001). In patients with BRCA1 negative tumours, low XRCC1 or low pol β expression was significantly associated with poor survival in univariate and multivariate analysis compared to high XRCC1 or high pol β expressing BRCA1 negative tumours (ps<0.05). Pre-clinically, BRCA1 negative cancer cells exhibit low mRNA and low protein expression of XRCC1 and pol β. BRCA1-BER deficient cells were sensitive to ATM and DNA-PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy

Cardiovascular Effects and Molecular Mechanisms of Bisphenol A and Its Metabolite MBP in Zebrafish

 This is the author accepted manuscript. The final version is available on open access from American Chemical Society via the DOI in this record The plastic monomer bisphenol A (BPA) is one of the highest production volume chemicals in the world and is frequently detected in wildlife and humans, particularly children. BPA has been associated with numerous adverse health outcomes relating to its estrogenic and other hormonal properties, but direct causal links are unclear in humans and animal models. Here we simulated measured (1×) and predicted worst-case (10×) maximum foetal exposures for BPA, or equivalent concentrations of its metabolite MBP, using fluorescent reporter embryo-larval zebrafish capable of quantifying Estrogen Response Element (ERE) activation throughout the body. Heart valves were primary sites for ERE activation by BPA and MBP, and transcriptomic analysis of micro-dissected heart tissues showed that both chemicals perturbed similar downstream molecular pathways and biological processes, including down-regulation of cartilage morphogenesis and filamentous protein synthesis. Collagen/keratin deficiency and impact on heart valve structural integrity were confirmed by histopathology for high-level MBP exposure, and structural defects (abnormal curvature) of the atrio-ventricular valves corresponded with impaired cardiovascular function (reduced ventricular beat rate and blood flow). Our results are the first to demonstrate plausible mechanistic links between ERE activation in the heart valves by BPA’s reactive metabolite MBP and the development of valvular- cardiovascular disease states.Biotechnology & Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC

Scholarly communication in transition: The use of question marks in the titles of scientific articles in medicine, life sciences and physics 1966–2005

The titles of scientific articles have a special significance. We examined nearly 20 million scientific articles and recorded the development of articles with a question mark at the end of their titles over the last 40 years. Our study was confined to the disciplines of physics, life sciences and medicine, where we found a significant increase from 50% to more than 200% in the number of articles with question-mark titles. We looked at the principle functions and structure of the titles of scientific papers, and we assume that marketing aspects are one of the decisive factors behind the growing usage of question-mark titles in scientific articles

Self-consistent solution of the Schwinger-Dyson equations for the nucleon and meson propagators

The Schwinger-Dyson equations for the nucleon and meson propagators are solved self-consistently in an approximation that goes beyond the Hartree-Fock approximation. The traditional approach consists in solving the nucleon Schwinger-Dyson equation with bare meson propagators and bare meson-nucleon vertices; the corrections to the meson propagators are calculated using the bare nucleon propagator and bare nucleon-meson vertices. It is known that such an approximation scheme produces the appearance of ghost poles in the propagators. In this paper the coupled system of Schwinger-Dyson equations for the nucleon and the meson propagators are solved self-consistently including vertex corrections. The interplay of self-consistency and vertex corrections on the ghosts problem is investigated. It is found that the self-consistency does not affect significantly the spectral properties of the propagators. In particular, it does not affect the appearance of the ghost poles in the propagators.Comment: REVTEX, 7 figures (available upon request), IFT-P.037/93, DOE/ER/40427-12-N9

Epistemic insights: Contemplating tensions between policy influences and creativity in school science

Creativity and the way it could be supported in schools is understood differently by policy makers, practitioners and scientists. This article reviews, with a chronological lens, the development of policies that include teaching creativity and teaching for creativity. The epistemic tensions between the intentions of government and the nature of creativity as it emerges in learning or scientific work is introduced and reflected upon. There have been more than nine key educational policies that have been introduced over the last 50 years. Each of these are considered in this article and related to the ways that creativity is understood and expected to be taught, supported or enacted in schools by policy makers. In light of the need to support creativity as a key twenty‐first‐century skill, to ultimately enable current students (who will become the next generation of scientists) to develop the capabilities to address global concerns, this article highlights issues related to this issue. Epistemic insights are offered that relate to the development of aspects of creativity, including questioning, developing alternate ideas, ‘seeing’ things differently, innovation, curiosity, problem solving and evaluating. The ways that policy related to creativity in science appears not to recognise how creativity can be reified in these ways in schools suggests the need for rapid review, especially in light of the upcoming international creativity tests in 2021