DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

Measurement of inclusive J/ψ suppression in Au+Au collisions at sNN=200 GeV through the dimuon channel at STAR

J/ψ suppression has long been considered a sensitive signature of the formation of the Quark-Gluon Plasma (QGP) in relativistic heavy-ion collisions. In this letter, we present the first measurement of inclusive J/ψ production at mid-rapidity through the dimuon decay channel in Au+Au collisions at sNN=200 GeV with the STAR experiment. These measurements became possible after the installation of the Muon Telescope Detector was completed in 2014. The J/ψ yields are measured in a wide transverse momentum (pT) range of 0.15 GeV/c to 12 GeV/c from central to peripheral collisions. They extend the kinematic reach of previous measurements at RHIC with improved precision. In the 0-10% most central collisions, the J/ψ yield is suppressed by a factor of approximately 3 for pT>5 GeV/c relative to that in p+p collisions scaled by the number of binary nucleon-nucleon collisions. The J/ψ nuclear modification factor displays little dependence on pT in all centrality bins. Model calculations can qualitatively describe the data, providing further evidence for the color-screening effect experienced by J/ψ mesons in the QGP

Charge-dependent pair correlations relative to a third particle in p + Au and d + Au collisions at RHIC

Quark interactions with topological gluon configurations can induce chirality imbalance and local parity violation in quantum chromodynamics. This can lead to electric charge separation along the strong magnetic field in relativistic heavy-ion collisions – the chiral magnetic effect (CME). We report measurements by the STAR collaboration of a CME-sensitive observable in p+Au and d+Au collisions at 200 GeV, where the CME is not expected, using charge-dependent pair correlations relative to a third particle. We observe strong charge-dependent correlations similar to those measured in heavy-ion collisions. This bears important implications for the interpretation of the heavy-ion data

A multicentre parallel-group randomised trial assessing multiparametric MRI characterisation and image-guided biopsy of prostate in men suspected of having prostate cancer:MULTIPROS study protocol

Background: There is growing evidence suggesting that multiparametric magnetic resonance imaging (mpMRI) is a marker for prostate cancer (PCa) aggressiveness and could be used to plan treatment. Improving early detection of clinically significant PCa with pre-biopsy mpMRI would very likely have advantages including optimising the diagnosis and treatment of diseases and diminishing patient anxiety.Methods and materials: This is a prospective multicentre study of pre-biopsy mpMRI diagnostic test accuracy with subgroup randomisation at a 1:1 ratio with respect to transrectal ultrasound (TRUS) and MRI/US fusion-guided biopsy or TRUS-only biopsy. It is designed as a single-gate study with a single set of inclusion criteria. The total duration of the recruitment phase was 48 months; however, this has now been extended to 66 months. A sample size of 600 participants is required.Discussion: The primary objective is to determine whether mpMRI can improve PCa detection and characterisation. The key secondary objective is to determine whether MRI/US fusion-guided biopsy can reduce the number of false-negative biopsies. Ethical approval was obtained from the East of Scotland Research Ethics Committee 1 (14/ES/1070) on 20 November 2014. The results of this study will be used for publication and presentation in national and international journals and at scientific conferences.Trial registration: ClinicalTrials.gov, NCT02745496. Retrospectively registered on 20 April 2016.</p

Measurements of the transverse-momentum-dependent cross sections of J /ψ production at mid-rapidity in proton+proton collisions at s =510 and 500 GeV with the STAR detector

We present measurements of the differential cross sections of inclusive J/ψ meson production as a function of transverse momentum (pTJ/ψ) using the μ+μ- and e+e- decay channels in proton+proton collisions at center-of-mass energies of 510 and 500 GeV, respectively, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The measurement from the μ+μ- channel is for

Bulk properties of the system formed in Au+Au collisions at sNN =14.5 GeV at the BNL STAR detector

We report systematic measurements of bulk properties of the system created in Au+Au collisions at sNN=14.5 GeV recorded by the STAR detector at the Relativistic Heavy Ion Collider (RHIC). The transverse momentum spectra of π±, K±, and p(p) are studied at midrapidity (|y|&lt;0.1) for nine centrality intervals. The centrality, transverse momentum (pT), and pseudorapidity (η) dependence of inclusive charged particle elliptic flow (v2), and rapidity-odd charged particles directed flow (v1) results near midrapidity are also presented. These measurements are compared with the published results from Au+Au collisions at other energies, and from Pb+Pb collisions at sNN=2.76 TeV. The results at sNN=14.5 GeV show similar behavior as established at other energies and fit well in the energy dependence trend. These results are important as the 14.5-GeV energy fills the gap in μB, which is of the order of 100 MeV, between sNN=11.5 and 19.6 GeV. Comparisons of the data with UrQMD and AMPT models show poor agreement in general

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A method for automatic segmentation and splitting of hyperspectral images of raspberry plants collected in field conditions

Abstract Hyperspectral imaging is a technology that can be used to monitor plant responses to stress. Hyperspectral images have a full spectrum for each pixel in the image, 400–2500 nm in this case, giving detailed information about the spectral reflectance of the plant. Although this technology has been used in laboratory-based controlled lighting conditions for early detection of plant disease, the transfer of such technology to imaging plants in field conditions presents a number of challenges. These include problems caused by varying light levels and difficulties of separating the target plant from its background. Here we present an automated method that has been developed to segment raspberry plants from the background using a selected spectral ratio combined with edge detection. Graph theory was used to minimise a cost function to detect the continuous boundary between uninteresting plants and the area of interest. The method includes automatic detection of a known reflectance tile which was kept constantly within the field of view for all image scans. A method to split images containing rows of multiple raspberry plants into individual plants was also developed. Validation was carried out by comparison of plant height and density measurements with manually scored values. A reasonable correlation was found between these manual scores and measurements taken from the images (r2 = 0.75 for plant height). These preliminary steps are an essential requirement before detailed spectral analysis of the plants can be achieved

Longitudinal double-spin asymmetry for inclusive jet and dijet production in pp collisions at s =510 GeV

We report the first measurement of the inclusive jet and the dijet longitudinal double-spin asymmetries, ALL, at midrapidity in polarized pp collisions at a center-of-mass energy s=510 GeV. The inclusive jet ALL measurement is sensitive to the gluon helicity distribution down to a gluon momentum fraction of x≈0.015, while the dijet measurements, separated into four jet-pair topologies, provide constraints on the x dependence of the gluon polarization. Both results are consistent with previous measurements made at s=200 GeV in the overlapping kinematic region, x&gt;0.05, and show good agreement with predictions from recent next-to-leading order global analyses

Differential lipid dependence of the function of bacterial sodium channels

The lipid bilayer is important for maintaining the integrity of cellular compartments and plays a vital role in providing the hydrophobic and charged interactions necessary for membrane protein structure, conformational flexibility and function. To directly assess the lipid dependence of activity for voltage-gated sodium channels, we compared the activity of three bacterial sodium channel homologues (NaChBac, NavMs, and NavSp) by cumulative 22Na+ uptake into proteoliposomes containing a 3:1 ratio of 1-palmitoyl 2-oleoyl phosphatidylethanolamine and different “guest” glycerophospholipids. We observed a unique lipid profile for each channel tested. NavMs and NavSp showed strong preference for different negatively-charged lipids (phosphatidylinositol and phosphatidylglycerol, respectively), whilst NaChBac exhibited a more modest variation with lipid type. To investigate the molecular bases of these differences we used synchrotron radiation circular dichroism spectroscopy to compare structures in liposomes of different composition, and molecular modeling and electrostatics calculations to rationalize the functional differences seen. We then examined pore-only constructs (with voltage sensor subdomains removed) and found that in these channels the lipid specificity was drastically reduced, suggesting that the specific lipid influences on voltage-gated sodium channels arise primarily from their abilities to interact with the voltage-sensing subdomains