171 research outputs found
Recommended from our members
Microbial Oxidation and Demethylation Processes in the Environmental Mercury Cycle
This project demonstrated that bacterial catalase enzymes can convert unreactive Hg(0) to highly reactive Hg(II) ion. It also demonstrated the mechanism of the organomercural lyase, a bacterial enzyme which degrades methylmercury and other organomercurials. Lastly, it demonstrated the 3-dimensional structure of this enzyme by both solution NMR and by x-ray crystallography. These structures provide insights into the catalytic mechanism of the lyase that will allow engineering of variants with improved ability to degrade methylmercury
Recommended from our members
Engineering MerR for Sequestration and MerA for Reduction of Toxic Metals and Radionuclides
The objectives of this project were (1) to alter a metalloregulatory protein (MerR) so that it would bind other toxic metals or radionuclides with similar affinity so that the engineered protein itself and/or bacteria expressing it could be deployed in the environment to specifically sequester such metals and (2) to alter the mercuric reductase, MerA, to reduce radionuclides and render them less mobile. Both projects had a basic science component. In the first case, such information about MerR illuminates how proteins discriminate very similar metals/elements. In the second case, information about MerA reveals the criteria for transmission of reducing equivalents from NADPH to redox-active metals. The work involved genetic engineering of all or parts of both proteins and examination of their resultant properties both in vivo and in vitro, the latter with biochemical and biophysical tools including equilibrium and non-equilibrium dialysis, XAFS, NMR, x-ray crystallography, and titration calorimetry. We defined the basis for metal specificity in MerR, devised a bacterial strain that sequesters Hg while growing, characterized gold reduction by MerA and the role of the metallochaperone domain of MerA, and determined the 3-D structure of MerB, the organomercurial lyase
The genomic basis of adaptive evolution in threespine sticklebacks
Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine–freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine–freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.National Human Genome Research Institute (U.S.)National Human Genome Research Institute (U.S.) (NHGRI CEGS Grant P50-HG002568
Proceedings of the International Cancer Imaging Society (ICIS) 16th Annual Teaching Course
Table of contents
O1 Tumour heterogeneity: what does it mean?
Dow-Mu Koh
O2 Skeletal sequelae in adult survivors of childhood cancer
Sue Creviston Kaste
O3 Locoregional effects of breast cancer treatment
Sarah J Vinnicombe
O4 Imaging of cancer therapy-induced CNS toxicity
Giovanni Morana, Andrea Rossi
O5 Screening for lung cancer
Christian J. Herold
O6Risk stratification of lung nodules
Theresa C. McLoud
O7 PET imaging of pulmonary nodules
Kirk A Frey
O8 Transarterial tumour therapy
Bernhard Gebauer
O9 Interventional radiology in paediatric oncology
Derek Roebuck
O10 Image guided prostate interventions
Jurgen J. Fütterer
O11 Imaging cancer predisposition syndromes
Alexander J. Towbin
O12Chest and chest wall masses
Thierry AG Huisman
O13 Abdominal masses: good or bad?
Anne MJB Smets
O14 Hepatobiliary MR contrast: enhanced liver MRI for HCC diagnosis and management
Giovanni Morana
O15 Role of US elastography and multimodality fusion for managing patients with chronic liver disease and HCC
Jeong Min Lee
O16 Opportunities and challenges in imaging metastatic disease
Hersh Chandarana
O17 Diagnosis, treatment monitoring, and follow-up of lymphoma
Marius E. Mayerhoefer, Markus Raderer, Alexander Haug
O18 Managing high-risk and advanced prostate cancer
Matthias Eiber
O19 Immunotherapy: imaging challenges
Bernhard Gebauer
O20 RECIST and RECIST 1.1
Andrea Rockall
O21 Challenges of RECIST in oncology imaging basics for the trainee and novice
Aslam Sohaib
O22 Lymphoma: PET for interim and end of treatment response assessment: a users’ guide to the Deauville Score
Victoria S Warbey
O23 Available resources
Hebert Alberto Vargas
O24 ICIS e-portal and the online learning community
Dow-Mu Koh
O25 Benign lesions that mimic pancreatic cancer
Jay P Heiken
O26 Staging and reporting pancreatic malignancies
Isaac R Francis, Mahmoud, M Al-Hawary, Ravi K Kaza
O27 Intraductal papillary mucinous neoplasm
Giovanni Morana
O28 Cystic pancreatic tumours
Mirko D’Onofrio
O29 Diffusion-weighted imaging of head and neck tumours
Harriet C. Thoeny
O30 Radiation injury in the head and neck
Ann D King
O31 PET/MR of paediatric brain tumours
Giovanni Morana, Arnoldo Piccardo, Maria Luisa Garrè, Andrea Rossi
O32 Structured reporting and beyond
Hebert Alberto Vargas
O33 Massachusetts General Hospital experience with structured reporting
Theresa C. McLoud
O34 The oncologist’s perspective: what the oncologist needs to know
Nick Reed
O35 Towards the cure of all children with cancer: global initiatives in pediatric oncology
Carlos Rodriguez-Galindo
O36 Multiparametric imaging of renal cancers
Hersh Chandarana
O37 Linking imaging features of renal disease and their impact on management strategies
Hebert Alberto Vargas
O38 Adrenals, retroperitoneum and peritoneum
Isaac R Francis, Ashish P Wasnik
O39 Lung and pleura
Stefan Diederich
O40 Advances in MRI
Jurgen J. Fütterer
O41 Advances in molecular imaging
Wim J.G. Oyen
O42 Incorporating advanced imaging, impact on treatment selection and patient outcome
Cheng Lee Chaw, Nicholas van As
S1 Combining ADC-histogram features improves performance of MR diffusion-weighted imaging for Lymph node characterisation in cervical cancer
Igor Vieira, Frederik De Keyzer, Elleke Dresen, Sileny Han, Ignace Vergote, Philippe Moerman, Frederic Amant, Michel Koole, Vincent Vandecaveye
S2 Whole-body diffusion-weighted MRI for surgical planning in patients with colorectal cancer and peritoneal metastases
R Dresen, S De Vuysere, F De Keyzer, E Van Cutsem, A D’Hoore, A Wolthuis, V Vandecaveye
S3 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extra capsular extension of prostate cancer.
P. Pricolo ([email protected]), S. Alessi, P. Summers, E. Tagliabue, G. Petralia
S4 Generating evidence for clinical benefit of PET/CT – are management studies sufficient as surrogate for patient outcome?
C. Pfannenberg, B. Gückel, SC Schüle, AC Müller, S. Kaufmann, N. Schwenzer, M. Reimold,C. la Fougere, K. Nikolaou, P. Martus
S5 Heterogeneity of treatment response in skeletal metastases from breast cancer with 18F-fluoride and 18F-FDG PET
GJ Cook, GK Azad, BP Taylor, M Siddique, J John, J Mansi, M Harries, V Goh
S6 Accuracy of suspicious breast imaging—can we tell the patient?
S Seth, R Burgul, A Seth
S7 Measurement method of tumour volume changes during neoadjuvant chemotherapy affects ability to predict pathological response
S Waugh, N Muhammad Gowdh, C Purdie, A Evans, E Crowe, A Thompson, S Vinnicombe
S8 Diagnostic yield of CT IVU in haematuria screening
F. Arfeen, T. Campion, E. Goldstraw
S9 Percutaneous radiofrequency ablation of unresectable locally advanced pancreatic cancer: preliminary results
D’Onofrio M, Ciaravino V, Crosara S, De Robertis R, Pozzi Mucelli R
S10 Iodine maps from dual energy CT improve detection of metastases in staging examinations of melanoma patients
M. Uhrig, D. Simons, H. Schlemmer
S11Can contrast enhanced CT predict pelvic nodal status in malignant melanoma of the lower limb?
Kate Downey
S12 Current practice in the investigation for suspected Paraneoplastic Neurological Syndromes (PNS) and positive malignancy yield.
S Murdoch, AS Al-adhami, S Viswanathan
P1 Technical success and efficacy of Pulmonary Radiofrequency ablation: an analysis of 207 ablations
S Smith, P Jennings, D Bowers, R Soomal
P2 Lesion control and patient outcome: prospective analysis of radiofrequency abaltion in pulmonary colorectal cancer metastatic disease
S Smith, P Jennings, D Bowers, R Soomal
P3 Hepatocellular carcinoma in a post-TB patient: case of tropical infections and oncologic imaging challenges
TM Mutala, AO Odhiambo, N Harish
P4 Role of apparent diffusion coefficient (ADC) diffusion-weighted MRI for predicting extracapsular extension of prostate cancer
P. Pricolo, S. Alessi, P. Summers, E. Tagliabue, G. Petralia
P5 What a difference a decade makes; comparison of lung biopsies in Glasgow 2005 and 2015
M. Hall, M. Sproule, S. Sheridan
P6 Solid pseudopapillary tumour of pancreas: imaging features of a rare neoplasm
KY Thein, CH Tan, YL Thian, CM Ho
P7 MDCT - pathological correlation in colon adenocarcinoma staging: preliminary experience
S De Luca, C Carrera, V Blanchet, L Alarcón, E Eyheremnedy
P8 Image guided biopsy of thoracic masses and reduction of pneumothorax risk: 25 years experience
B K Choudhury, K Bujarbarua, G Barman
P9 Tumour heterogeneity analysis of 18F-FDG-PET for characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1
GJ Cook, E Lovat, M Siddique, V Goh, R Ferner, VS Warbey
P10 Impact of introduction of vacuum assisted excision (VAE) on screen detected high risk breast lesions
L Potti, B Kaye, A Beattie, K Dutton
P11 Can we reduce prevalent recall rate in breast screening?
AA Seth, F Constantinidis, H Dobson
P12 How to reduce prevalent recall rate? Identifying mammographic lesions with low Positive Predictive Value (PPV)
AA Seth ([email protected]), F Constantinidis, H Dobson
P13 Behaviour of untreated pulmonary thrombus in oncology patients diagnosed with incidental pulmonary embolism on CT
R. Bradley, G. Bozas, G. Avery, A. Stephens, A. Maraveyas
P14 A one-stop lymphoma biopsy service – is it possible?
S Bhuva, CA Johnson, M Subesinghe, N Taylor
P15 Changes in the new TNM classification for lung cancer (8th edition, effective January 2017)
LE Quint, RM Reddy, GP Kalemkerian
P16 Cancer immunotherapy: a review of adequate imaging assessment
G González Zapico, E Gainza Jauregui, R Álvarez Francisco, S Ibáñez Alonso, I Tavera Bahillo, L Múgica Álvarez
P17 Succinate dehydrogenase mutations and their associated tumours
O Francies, R Wheeler, L Childs, A Adams, A Sahdev
P18 Initial experience in the usefulness of dual energy technique in the abdomen
SE De Luca, ME Casalini Vañek, MD Pascuzzi, T Gillanders, PM Ramos, EP Eyheremendy
P19 Recognising the serious complication of Richter’s transformation in CLL patients
C Stove, M Digby
P20 Body diffusion-weighted MRI in oncologic practice: truths, tricks and tips
M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy
P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients
D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein
P22 Pitfalls in oncology CT reporting. A pictorial review
R Rueben, S Viswanathan
P23 Imaging of perineural extension in head and neck tumours
B Nazir, TH Teo, JB Khoo
P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer
K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins
P25 When cancer can’t wait! A pictorial review of oncological emergencies
K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua
P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation
D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh
P27 Gynaecological cancers in pregnancy: a review of imaging
CA Johnson, J Lee
P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart
JA Goodfellow, AS Al-adhami, S Viswanathan
P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy
R Bradley
P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience
R Bradley
P31 Radiological assessment of the post-chemotherapy liver
A Yong, S Jenkins, G Joseph
P32 Skeletal staging with MRI in breast cancer – what the radiologist needs to know
S Bhuva, K Partington
P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease
CA Johnson, S Bhuva, M Subesinghe, N Taylor
P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools.
C Carrera, A Zanfardini, S De Luca, L Alarcón, V Blanchet, EP Eyheremendy
P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test?
K Cavanagh, E Lauhttp://deepblue.lib.umich.edu/bitstream/2027.42/134651/1/40644_2016_Article_79.pd
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 × 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe
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