61 research outputs found
Cost-effectiveness analysis of anal cancer screening in women with cervical neoplasia in British Columbia, Canada
- Author
- AJCC
- AM Saleem
- C. Aquino-Parsons
- D Tsoi
- DA Machalek
- DA Machalek
- DP Ryan
- EA Holly
- EL Conway
- G Edgren
- GB Lazenby
- HE Uronis
- HS Evans
- I Kalliala
- I. Cromwell
- J Bentley
- J Karnon
- J Melnikow
- J Melnikow
- JH Scholefield
- JM Palefsky
- JT Santoso
- LS Massad
- M Gaudet
- M Sadatsafavi
- M. Gaudet
- MA Stanley
- MA Vink
- MF Drummond
- MT Goodman
- NA Hessol
- RP Insinga
- S Feig
- S. J. Peacock
- SB Cantor
- SJ Goldie
- W Jimenez
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection
- Author
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 12/07/2023
- Field of study
Understanding protective immunity to COVID-19 facilitates preparedness for future pandemics and combats new SARS-CoV-2 variants emerging in the human population. Neutralizing antibodies have been widely studied; however, on the basis of large-scale exome sequencing of protected versus severely ill patients with COVID-19, local cell-autonomous defence is also crucial1,2,3,4. Here we identify phospholipid scramblase 1 (PLSCR1) as a potent cell-autonomous restriction factor against live SARS-CoV-2 infection in parallel genome-wide CRISPR–Cas9 screens of human lung epithelia and hepatocytes before and after stimulation with interferon-γ (IFNγ). IFNγ-induced PLSCR1 not only restricted SARS-CoV-2 USA-WA1/2020, but was also effective against the Delta B.1.617.2 and Omicron BA.1 lineages. Its robust activity extended to other highly pathogenic coronaviruses, was functionally conserved in bats and mice, and interfered with the uptake of SARS-CoV-2 in both the endocytic and the TMPRSS2-dependent fusion routes. Whole-cell 4Pi single-molecule switching nanoscopy together with bipartite nano-reporter assays found that PLSCR1 directly targeted SARS-CoV-2-containing vesicles to prevent spike-mediated fusion and viral escape. A PLSCR1 C-terminal β-barrel domain—but not lipid scramblase activity—was essential for this fusogenic blockade. Our mechanistic studies, together with reports that COVID-associated PLSCR1 mutations are found in some susceptible people3,4, identify an anti-coronavirus protein that interferes at a late entry step before viral RNA is released into the host-cell cytosol
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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- A. -G. Wu
- A. C. Ma
- A. K. Au
- Abdel-Aziz A. K.
- Abdelfatah S.
- Abdellatif M.
- Abdoli A.
- Abel S.
- Abeliovich H.
- Abildgaard M. H.
- Abudu Y. P.
- Acevedo-Arozena A.
- Adamopoulos I. E.
- Adeli K.
- Adolph T. E.
- Adornetto A.
- Aflaki E.
- Agam G.
- Agarwal A.
- Aggarwal B. B.
- Agnello M.
- Agostinis P.
- Agrewala J. N.
- Agrotis A.
- Aguilar P. V.
- Ahmad S. T.
- Ahmed Z. M.
- Ahumada-Castro U.
- Aits S.
- Aizawa S.
- Akkoc Y.
- Akoumianaki T.
- Akpinar H. A.
- Al-Abd A. M.
- Al-Akra L.
- Al-Gharaibeh A.
- Alaoui-Jamali M. A.
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- Alcocer-Gomez E.
- Alessandri C.
- Ali M.
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- Aliwaini S.
- Alizadeh J.
- Almacellas E.
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Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.
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- A Cox
- A Siddiq
- AC Antoniou
- Aida Karina Dieffenbach
- Alan Ashworth
- Alexander Hein
- Alfons Meindl
- Alice S Whittemore
- Alison M Dunning
- Amanda E Toland
- Angela Cox
- Anja Rudolph
- Anna González-Neira
- Anna H Wu
- Anna Jakubowska
- Anna Marie Mulligan
- Annegien Broeks
- Annika Lindblom
- Anthony J Swerdlow
- Antoinette Hollestelle
- Arja Jukkola-Vuorinen
- Artitaya Lophatananon
- Arto Mannermaa
- B Howie
- Barbara Burwinkel
- Barbara J Perkins
- Brian E Henderson
- Børge G Nordestgaard
- C Turnbull
- CA Haiman
- Carl Blomqvist
- Carmel Apicella
- Caroline Baynes
- Caroline Seynaeve
- Catherine S Healey
- Catriona McLean
- Celine Vachon
- Chen-Yang Shen
- Cheng Har Yip
- Chia-Ni Hsiung
- Ching Wan Chan
- Chiu-chen Tseng
- Christa Stegmaier
- Christi J Van Asperen
- Christian Sutter
- Christine B Ambrosone
- Christine D Berg
- Christof Sohn
- Christopher A Haiman
- CJ Willer
- Claire Mulot
- Clare Turnbull
- Craig Luccarini
- D Hnisz
- Daehee Kang
- Daniel C Tessier
- Daniel F Schmidt
- Daniel Herrero
- Daniel O Stram
- Daniel Vincent
- David J Hunter
- David Van Den Berg
- DF Easton
- DF Gudbjartsson
- Diana Torres
- Dieter Flesch-Janys
- Diether Lambrechts
- Dimitrios Trichopoulos
- DJ Hunter
- Domenico Palli
- Douglas F Easton
- Drakoulis Yannoukakos
- Eiliv Lund
- Elinor J Sawyer
- Emily Hallberg
- Enes Makalic
- Erik van Limbergen
- Esther M John
- F Kamangar
- Federico Canzian
- Fergus J Couch
- France Labrèche
- Francois Bacot
- Frederik Marme
- Fredrick Schumacher
- G Thomas
- Georgia Chenevix-Trench
- Gie-Hooi Tan
- Giske Ursin
- Gord Glendon
- Graham Casey
- Graham G Giles
- Grethe I Grenaker Alnaes
- Guillermo Pita
- H Ahsan
- H Kim
- H Meijers-Heijboer
- Habibul Ahsan
- Hanne Meijers-Heijboer
- Hans Wildiers
- Harald Surowy
- Hatef Darabi
- Helen Tsimiklis
- Heli Nevanlinna
- Henrik Flyger
- Hermann Brenner
- Hidemi Ito
- Hiltrud Brauch
- Hiroji Iwata
- Hoda Anton-Culver
- Hui Cai
- Hui Miao
- Ian Tomlinson
- Irene L Andrulis
- Isabel dos-Santos-Silva
- J Long
- J Marchini
- J Margriet Collée
- Jaana M Hartikainen
- Jacques Simard
- James McKay
- Jan Lubinski
- Janet E Olson
- Javier Benitez
- Jenny Chang-Claude
- Ji-Yeob Choi
- Jianjun Liu
- Jingmei Li
- Jirong Long
- Joe Dennis
- John L Hopper
- John W M Martens
- Jonathan Beesley
- Jonine Figueroa
- Jose Ignacio Arias Perez
- Jose-Maria Huerta
- Judith S Brand
- Julia A Knight
- Julian Peto
- K Michailidou
- Kamila Czene
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- Kathleen E Malone
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- Robert Winqvist
- Roger L Milne
- Rongxi Yang
- S Ahmed
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- Sara Lindstrom
- Sara Margolin
- Sarah Stewart-Brown
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- Silje Nord
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- Siranoush Manoukian
- SN Stacey
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- Suleeporn Sangrajrang
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- Susan M Gapstur
- Susan Slager
- Taru A Muranen
- Thilo Dörk
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- Publication venue
- Nat Genet
- Publication date
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- Field of study
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.BCAC is funded by Cancer Research UK (C1287/A10118, C1287/A12014) and by the European Community's Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS). Meetings of the BCAC have been funded by the European Union COST programme (BM0606). Genotyping on the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710, C8197/A16565), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program and the Ministry of Economic Development, Innovation and Export Trade of Quebec, grant PSR-SIIRI-701. Combination of the GWAS data was supported in part by the US National Institutes of Health (NIH) Cancer Post-Cancer GWAS initiative, grant 1 U19 CA148065-01 (DRIVE, part of the GAME-ON initiative). For a full description of funding and acknowledgments, see the Supplementary Note.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.324
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- Zhu B
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- Zhu G-Q
- Zhu H
- Zhu H
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- Zhuang H
- Zhuang X
- Zientara-Rytter K
- Zimmermann CM
- Ziviani E
- Zoladek T
- Zong W-X
- Zorov DB
- Zorzano A
- Zou W
- Zou Z
- Zou Z
- Zuryn S
- Zwerschke W
- Álvarez ÉMC
- Ávalos Y
- Önal G
- Üstün S
- Čolić M
- Đokić J
- Žerovnik E
- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2021
- Field of study
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field
Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells
- Author
- A Celeste
- A Dobin
- A Meissner
- A Nagy
- A Raggioli
- A Tarasov
- A Xiao
- AA Kolodziejczyk
- Aaron J. Huebner
- Alexander Meissner
- Andreas Gnirke
- Andrej Savol
- Andrew Xiao
- Arman Mohammad
- B Langmead
- Bruno Di Stefano
- C Tamm
- Christopher M. Rose
- CY McLean
- D Dutta
- E Habibi
- EG Schulz
- EL Huttlin
- F Gaudet
- G Ficz
- H Chen
- H Li
- H Marks
- Haruhiko Koseki
- HG Leitch
- Hongcang Gu
- I Zvetkova
- J Choi
- J Wray
- JA Hackett
- Jafar Sharif
- JE Dodge
- JE Elias
- Jean Charron
- Jiho Choi
- JK Eng
- JT Robinson
- Junko Odajima
- Justin Brumbaugh
- K Eggan
- Kaixuan Lin
- Kendell Clement
- Konrad Hochedlinger
- M Kaneda
- M Stadtfeld
- MD Robinson
- NR Treff
- P Boyle
- Q Song
- Q-L Ying
- RN Plasschaert
- Ruslan I. Sadreyev
- Ryan M. Walsh
- RZ Chen
- S Anders
- S Anders
- Sang-Yong Kim
- Steven Gygi
- T Shimizu
- T Wu
- TM Keane
- Toshi Shioda
- TW Theunissen
- von F Meyenn
- WA Pastor
- Y Takashima
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- Field of study
Common germline polymorphisms associated with breast cancer-specific survival
- Author
- A Beeghly-Fadiel
- A Beeghly-Fadiel
- A Gerger
- A Siddiq
- Ailith Pirie
- Alexander Hein
- Alison M Dunning
- Andreas Schneeweiss
- Angela Cox
- Anika Hüsing
- Anja Rudolph
- Anna Jakubowska
- Anna Marie Mulligan
- Annegien Broeks
- Ans MW van den Ouweland
- Antoinette Hollestelle
- Arif B Ekici
- Arja Jukkola-Vuorinen
- Arto Mannermaa
- Barbara Burwinkel
- Bernd Holleczek
- Brian E Henderson
- Børge G Nordestgaard
- C Curtis
- C Duggan
- Carl Blomqvist
- Carlos Caldas
- Carmel Apicella
- Caroline Seynaeve
- Caroline Weltens
- Catriona McLean
- Celine Vachon
- Chantal van Ongeval
- Christopher A Haiman
- Christopher J Poole
- CJ Poole
- CJ Poole
- Constance Chen
- CX Yang
- D Eccles
- D Gareth Evans
- Daniele Campa
- David J Hunter
- Diana M Eccles
- Dieter Flesch-Janys
- Dieter Lambrechts
- DJ Hunter
- DN Martin
- Douglas F Easton
- E Castro
- EK Bryant
- EL Goode
- Elinor J Sawyer
- EM Azzato
- EM Azzato
- EM Azzato
- Emily Hallberg
- F Otterbach
- Federick Marme
- Federico Canzian
- Fergus J Couch
- Filomena Ficarazzi
- Frederick Schumacher
- GC Wishart
- Georgia Chenevix-Trench
- Gord Glendon
- Graham G Giles
- H Lu
- Hans Ulrich Ulmer
- Hatef Darabi
- Helen Tsimiklis
- Helena Earl
- Heli Nevanlinna
- Henrik Flyger
- Hermann Brenner
- HM Earl
- Ian Tomlinson
- Irene L Andrulis
- J Decock
- J Tommiska
- Jaana M Hartikainen
- Jacek Gronwald
- Jan Lubinski
- Janet A Dunn
- Janet E Olsen
- Javier Benitez
- JE Abraham
- Jean Abraham
- Jenny Chang-Claude
- JH Lee
- Jingmei Li
- JM Hartikainen
- Joe Dennis
- John L Hopper
- John WM Martens
- Jolanta Lissowska
- Jonathan Tyrer
- Jonine Figueroa
- Jose Ignacio Arias Perez
- JR Long
- JR Long
- Judith S Brand
- Julia A Knight
- JY Choi
- JY Choi
- K Buck
- K Einarsdóttir
- K Michailidou
- Kamila Czene
- Karin Leunen
- Katarzyna Durda
- Katja Butterbach
- Katri Pylkäs
- Keith Humphreys
- Kelly-Anne Phillips
- Kristiina Aittomäki
- Kyriaki Michailidou
- L Jiang
- L Perna
- Loic Le Marchand
- Louise Hiller
- M Hartman
- M Jamshidi
- M Pande
- M Pilar Zamora
- MA Bewick
- MA Bewick
- Maartje J Hooning
- Malcolm WR Reed
- Manjeet K Bolla
- Maria Kabisch
- Marjanka K Schmidt
- Matthias W Beckmann
- Melissa C Southey
- Mervi Grip
- Mia M Gaudet
- Michael J Kerin
- Michael Lush
- Mikael Eriksson
- Mitchell J Machiela
- Mitul Shah
- MK Schmidt
- ML Slattery
- Montserrat Garcia-Closas
- Myrto Barrdahl
- N Ribelles
- Nazneen Rahman
- NB Peterson
- Nicola Miller
- P Fasching
- P Kontogianni
- PA Fasching
- Paolo Peterlongo
- Paolo Radice
- Paul DP Pharoah
- PDP Pharoah
- Per Hall
- Peter A Fasching
- Peter Devilee
- Peter Kraft
- Petra Seibold
- Primitiva Menéndez
- Qi Guo
- Qin Wang
- R Fagerholm
- R Pei
- R Upadhyay
- Rainer Fagerholm
- Robert AEM Tollenaar
- Robert N Hoover
- Robert Winqvist
- Roger L Milne
- Rongxi Yang
- Rose Yang
- Rosemary Balleine
- Rudolf Kaaks
- S Bayraktar
- S Qu
- Sander Canisius
- Sara Lindstrom
- Sara Margolin
- Sarah Bowden
- Siljie Nord
- Simon S Cross
- Siranoush Manoukian
- Sofia Khan
- Sten Cornelissen
- Stephen J Chanock
- Stig E Bojesen
- Suet-Feung Chin
- Sune F Nielsen
- Susan Hankinson
- Susan M Gapstur
- T Toyama
- Taru A Muranen
- Thomas Rüdiger
- Ute Hamann
- Veli-Matti Kosma
- Vesa Kataja
- Vessela Kristensen
- W Ryan Diver
- Walter Willett
- WY Lin
- XO Shu
- XO Shu
- Y You
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2015
- Field of study
Abstract
Introduction
Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.
Methods
A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect.
Results
Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease.
Conclusions
Although no variants reached genome-wide significance (P <5 x 10−8), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels
Host recognition of the bacterial metabolite HBP.
- Publication venue
- Publication date
- Field of study
<p>(<b>A</b>) Gram-negative bacteria possess a unique branch from the pentose phosphate pathway (PPP) that generates ADP- heptose precursors (ADP-hep) for incorporation of heptose (green hexagon) into the inner core of the LPS structure. Hep-1,7-PP (HBP) is synthesized in the second step of this pathway and is released from bacteria during growth or lysis. (<b>B</b>) Summary of the manners by which gram-negative bacteria can present HBP to mammalian cells and activate the TIFA-signaling pathway. TIFA is an intrinsic anti-parallel dimer, possessing a Threonine residue (Thr9), a central forkhead domain (FHA), and a C-terminal TRAF6 binding site (T6BP; green rectangle). Upon HBP detection, Thr9 is phosphorylated, driving head-to tail oligomerization via intermolecular pThr9-FHA interactions. TIFA oligomers or the ‘TIFAsome’ recruits and activates TRAF6, driving canonical NF-κB activation and inflammatory signaling. Inset fluorescence micrograph depicts HBP-induced TIFAsome formation (green, white arrow) in human colonic epithelial cells treated with HBP for 2 hours. Nucleus is stained with DAPI (blue), scale bar 5 μm.</p
Molecular characterization of the cervical and systemic B-cell repertoire
- Author
- Publication venue
- 'Informa UK Limited'
- Publication date
- Field of study
- …