Weekly platinum chemotherapy for recurrent ovarian cancer

British Journal of Cancer (2002) 86, 2–4. DOI: 10.1038/sj/bjc/6600062 www.bjcancer.co

The Spin Structure of the Nucleon

We present an overview of recent experimental and theoretical advances in our understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure

Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death

Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca2+ fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca2+ influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca2+ fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins

Ensembl’s 10th year

Ensembl (http://www.ensembl.org) integrates genomic information for a comprehensive set of chordate genomes with a particular focus on resources for human, mouse, rat, zebrafish and other high-value sequenced genomes. We provide complete gene annotations for all supported species in addition to specific resources that target genome variation, function and evolution. Ensembl data is accessible in a variety of formats including via our genome browser, API and BioMart. This year marks the tenth anniversary of Ensembl and in that time the project has grown with advances in genome technology. As of release 56 (September 2009), Ensembl supports 51 species including marmoset, pig, zebra finch, lizard, gorilla and wallaby, which were added in the past year. Major additions and improvements to Ensembl since our previous report include the incorporation of the human GRCh37 assembly, enhanced visualisation and data-mining options for the Ensembl regulatory features and continued development of our software infrastructure

PET/MR imaging of bone lesions - implications for PET quantification from imperfect attenuation correction

PURPOSE: Accurate attenuation correction (AC) is essential for quantitative analysis of PET tracer distribution. In MR, the lack of cortical bone signal makes bone segmentation difficult and may require implementation of special sequences. The purpose of this study was to evaluate the need for accurate bone segmentation in MR-based AC for whole-body PET/MR imaging. METHODS: In 22 patients undergoing sequential PET/CT and 3-T MR imaging, modified CT AC maps were produced by replacing pixels with values of >100 HU, representing mostly bone structures, by pixels with a constant value of 36 HU corresponding to soft tissue, thereby simulating current MR-derived AC maps. A total of 141 FDG-positive osseous lesions and 50 soft-tissue lesions adjacent to bones were evaluated. The mean standardized uptake value (SUVmean) was measured in each lesion in PET images reconstructed once using the standard AC maps and once using the modified AC maps. Subsequently, the errors in lesion tracer uptake for the modified PET images were calculated using the standard PET image as a reference. RESULTS: Substitution of bone by soft tissue values in AC maps resulted in an underestimation of tracer uptake in osseous and soft tissue lesions adjacent to bones of 11.2 ± 5.4 % (range 1.5-30.8 %) and 3.2 ± 1.7 % (range 0.2-4 %), respectively. Analysis of the spine and pelvic osseous lesions revealed a substantial dependence of the error on lesion composition. For predominantly sclerotic spine lesions, the mean underestimation was 15.9 ± 3.4 % (range 9.9-23.5 %) and for osteolytic spine lesions, 7.2 ± 1.7 % (range 4.9-9.3 %), respectively. CONCLUSION: CT data simulating treating bone as soft tissue as is currently done in MR maps for PET AC leads to a substantial underestimation of tracer uptake in bone lesions and depends on lesion composition, the largest error being seen in sclerotic lesions. Therefore, depiction of cortical bone and other calcified areas in MR AC maps is necessary for accurate quantification of tracer uptake values in PET/MR imaging

TESS Delivers Five New Hot Giant Planets Orbiting Bright Stars From The Full-Frame Images

We present the discovery and characterization of five hot and warm Jupiters—TOI-628 b (TIC 281408474; HD 288842), TOI-640 b (TIC 147977348), TOI-1333 b (TIC 395171208, BD+47 3521A), TOI-1478 b (TIC 409794137), and TOI-1601 b (TIC 139375960)—based on data from NASA\u27s Transiting Exoplanet Survey Satellite (TESS). The five planets were identified from the full-frame images and were confirmed through a series of photometric and spectroscopic follow-up observations by the TESS Follow-up Observing Program Working Group. The planets are all Jovian size (RP = 1.01–1.77 RJ) and have masses that range from 0.85 to 6.33 MJ. The host stars of these systems have F and G spectral types (5595 ≤ Teff ≤ 6460 K) and are all relatively bright (9.5 \u3c V \u3c 10.8, 8.2 \u3c K \u3c 9.3), making them well suited for future detailed characterization efforts. Three of the systems in our sample (TOI-640 b, TOI-1333 b, and TOI-1601 b) orbit subgiant host stars ($\mathrm{log}$ g \u3c 4.1). TOI-640 b is one of only three known hot Jupiters to have a highly inflated radius (RP \u3e 1.7 RJ, possibly a result of its host star\u27s evolution) and resides on an orbit with a period longer than 5 days. TOI-628 b is the most massive, hot Jupiter discovered to date by TESS with a measured mass of ${6.31}_{-0.30}^{+0.28}$MJ and a statistically significant, nonzero orbital eccentricity of e = ${0.074}_{-0.022}^{+0.021}$. This planet would not have had enough time to circularize through tidal forces from our analysis, suggesting that it might be remnant eccentricity from its migration. The longest-period planet in this sample, TOI-1478 b (P = 10.18 days), is a warm Jupiter in a circular orbit around a near-solar analog. NASA\u27s TESS mission is continuing to increase the sample of well-characterized hot and warm Jupiters, complementing its primary mission goals

Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace

Integrative analysis of multiple data types to address complex biomedical questions requires the use of multiple software tools in concert and remains an enormous challenge for most of the biomedical research community. Here we introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource. Seeded as a collaboration of six of the most popular genomics analysis tools, GenomeSpace now supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate the ability of non-programming users’ to leverage GenomeSpace in integrative analysis, it offers a growing set of ‘recipes’, short workflows involving a few tools and steps to guide investigators through high utility analysis tasks

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Correction to: 2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Archives of Virology (2021) 166:3567–3579. https://doi.org/10.1007/s00705-021-05266-wIn March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.This work was supported in part through Laulima Government Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC under Contract No. HHSN272201800013C. This work was also supported in part with federal funds from the National Cancer Institute (NCI), National Institutes of Health (NIH), under Contract No. 75N91019D00024, Task Order No. 75N91019F00130 to I.C., who was supported by the Clinical Monitoring Research Program Directorate, Frederick National Lab for Cancer Research. This work was also funded in part by Contract No. HSHQDC-15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges partial support from the Special Research Initiative of Mississippi Agricultural and Forestry Experiment Station (MAFES), Mississippi State University, and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project 1021494. Part of this work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK (FC001030), the UK Medical Research Council (FC001030), and the Wellcome Trust (FC001030).S