| 1. |
- Van Deerlin, Vivian M, et al.
(författare)
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Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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| 2. |
- Hansen, Jonah T., et al.
(författare)
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The Pyxis Interferometer (I) : Scientific Context, Metrology System and Optical Design
- 2022
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Ingår i: Optical and infrared interferometry and imaging VIII. - : SPIE - International Society for Optical Engineering. - 9781510653481 - 9781510653474
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Konferensbidrag (refereegranskat)abstract
- Optical interferometry from space is arguably the most exciting prospect for high angular resolution astrophysics; including the analysis of exoplanet atmospheres. This was highlighted in the recent ESA Voyage 2050 plan, which pointed out the exciting potential of this technology, but also indicated the critical need for technological demonstrators. Here we present the Pyxis interferometer; a ground-based pathfinder for a CubeSat space interferometer, currently being built at Mt Stromlo Observatory. We outline its technological and scientific potential as the only visible wavelength interferometer in the Southern Hemisphere, and the optical systems designed to provide CubeSat compatible metrology for formation flying.
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| 3. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 4. |
- Ajore, Ram, et al.
(författare)
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Deletion of ribosomal protein genes is a common vulnerability in human cancer, especially in concert with TP53 mutations
- 2017
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4684 .- 1757-4676. ; 9:4, s. 498-507
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10−10), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells. In contrast, we did not see negative selection of RPG deletions in TP53-mutant tumors. RPGs are conserved with respect to homozygous deletions, and shRNA screening data from 174 cell lines demonstrate that further suppression of hemizygously deleted RPGs inhibits cell growth. Our results establish RPG haploinsufficiency as a strikingly common vulnerability of human cancers that associates with TP53 mutations and could be targetable therapeutically.
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| 5. |
- Ariens, Robert, et al.
(författare)
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Illustrated State-of-the-Art Capsules of the ISTH 2020 Congress
- 2020
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Ingår i: RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS. - : Wiley. - 2475-0379. ; 4:5, s. 680-713
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Forskningsöversikt (refereegranskat)abstract
- The 2020 Congress of the International Society of Thrombosis and Haemostasis (ISTH) was held virtually July 12-15, 2019, due to the coronavirus disease 2019 pandemic. The congress convenes annually to discuss clinical and basic topics in hemostasis and thrombosis. Each year, the program includes State of Art (SOA) lectures given by prominent scientists. Presenters are asked to create Illustrated Capsules of their talks, which are concise illustrations with minimal explanatory text. Capsules cover major themes of the presentation, and these undergo formal peer review for inclusion in this article. Owing to the shift to a virtual congress this year, organizers reduced the program size. There were 39 SOA lectures virtually presented, and 29 capsules (9 from talks omitted from the virtual congress) were both submitted and successful in peer review, and are included in this article. Topics include the roles of the hemostatic system in inflammation, infection, immunity, and cancer, platelet function and signaling, platelet function disorders, megakaryocyte biology, hemophilia including gene therapy, phenotype tests in hemostasis, von Willebrand factor, anticoagulant factor V, computational driven discovery, endothelium, clinical and basic aspects of thrombotic microangiopathies, fibrinolysis and thrombolysis, antithrombotics in pediatrics, direct oral anticoagulant management, and thrombosis and hemostasis in pregnancy. Capsule authors invite virtual congress attendees to refer to these capsules during the live presentations and participate on Twitter in discussion. Research and Practice in Haemostasis and Thrombosis will release 2 tweets from @RPTHJournal during each presentation, using #IllustratedReview, #CoagCapsule and #ISTH2020. Readers are also welcome to utilize capsules for teaching and ongoing education.
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| 6. |
- Aronson, Richard, et al.
(författare)
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No barrier to emergence of bathyal king crabs on the Antarctic shelf
- 2015
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Ingår i: Proceedings of the National Academy of Science of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:42, s. 12997-13002
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Tidskriftsartikel (refereegranskat)abstract
- Cold-water conditions have excluded durophagous (skeleton-breaking) predators from the Antarctic seafloor for millions of years. Rapidly warming seas off the western Antarctic Peninsula could now facilitate their return to the continental shelf, with profound consequences for the endemic fauna. Among the likely first arrivals are king crabs (Lithodidae), which were discovered recently on the adjacent continental slope. During the austral summer of 2010‒2011, we used underwater imagery to survey a slope-dwelling population of the lithodid Paralomis birsteini off Marguerite Bay, western Antarctic Peninsula for environmental or trophic impediments to shoreward expansion. The population density averaged ∼4.5 individuals × 1,000 m−2 within a depth range of 1,100‒1,500 m (overall observed depth range 841–2,266 m). Images of juveniles, discarded molts, and precopulatory behavior, as well as gravid females in a trapping study, suggested a reproductively viable population on the slope. At the time of the survey, there was no thermal barrier to prevent the lithodids from expanding upward and emerging on the outer shelf (400- to 550-m depth); however, near-surface temperatures remained too cold for them to survive in inner-shelf and coastal environments (<200 m). Ambient salinity, composition of the substrate, and the depth distribution of potential predators likewise indicated no barriers to expansion of lithodids onto the outer shelf. Primary food resources for lithodids—echinoderms and mollusks—were abundant on the upper slope (550–800 m) and outer shelf. As sea temperatures continue to rise, lithodids will likely play an increasingly important role in the trophic structure of subtidal communities closer to shore.
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| 7. |
- Ashton, Nicholas J., et al.
(författare)
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A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer's disease.
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- A blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer's disease (AD) therapeutic trials. In this study, cognitively unimpaired individuals from the AIBL and KARVIAH cohorts were defined as Aβ negative or Aβ positive by positron emission tomography. Nontargeted proteomic analysis that incorporated peptide fractionation and high-resolution mass spectrometry quantified relative protein abundances in plasma samples from all participants. A protein classifier model was trained to predict Aβ-positive participants using feature selection and machine learning in AIBL and independently assessed in KARVIAH. A 12-feature model for predicting Aβ-positive participants was established and demonstrated high accuracy (testing area under the receiver operator characteristic curve = 0.891, sensitivity = 0.78, and specificity = 0.77). This extensive plasma proteomic study has unbiasedly highlighted putative and novel candidates for AD pathology that should be further validated with automated methodologies.
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| 8. |
- Ban, Nenad, et al.
(författare)
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A new system for naming ribosomal proteins.
- 2014
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Ingår i: Current Opinion in Structural Biology. - : Elsevier BV. - 1879-033X .- 0959-440X. ; 24, s. 165-169
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Tidskriftsartikel (refereegranskat)abstract
- A system for naming ribosomal proteins is described that the authors intend to use in the future. They urge others to adopt it. The objective is to eliminate the confusion caused by the assignment of identical names to ribosomal proteins from different species that are unrelated in structure and function. In the system proposed here, homologous ribosomal proteins are assigned the same name, regardless of species. It is designed so that new names are similar enough to old names to be easily recognized, but are written in a format that unambiguously identifies them as 'new system' names.
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| 9. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 10. |
- Beck, R., et al.
(författare)
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GPSDTN : Predictive velocity-enabled delay-tolerant networks for arctic research and sustainability
- 2007
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Ingår i: Second International Conference on Internet Monitoring and Protection (ICIMP 2007). - Los Alamitos, Calif : IEEE Computer Society Press. - 9780769529110
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Konferensbidrag (refereegranskat)abstract
- A Delay-Tolerant Network (DTN) is a necessity for communication nodes that may need to wait for long periods to form networks. The IETF Delay Tolerant Network Research Group is developing protocols to enable such networks for a broad variety of Earth and interplanetary applications. The Arctic would benefit from a predictive velocity-enabled version of DTN that would facilitate communications between sparse, ephemeral, often mobile and extremely power-limited nodes. We propose to augment DTN with power-aware, buffer-aware location- and time-based predictive routing for ad-hoc meshes to create networks that are inherently location and time (velocity) aware at the network level to support climate research, emergency services and rural education in the Arctic. On Earth, the primary source of location and universal time information for networks is the Global Positioning System (GPS). We refer to this Arctic velocity-enabled Delay-Tolerant Network protocol as "GPSDTN" accordingly. This paper describes our requirements analysis and general implementation strategy for GPSDTN to support Arctic research and sustainability efforts
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