| 1. |
- 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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| 2. |
- Richards, Stephen, et al.
(författare)
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Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
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Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
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Tidskriftsartikel (refereegranskat)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
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| 3. |
- Gu, Thomas, et al.
(författare)
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Symptomatic carotid near-occlusion causes a high risk of recurrent ipsilateral ischemic stroke
- 2020
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Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 267, s. 522-530
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the risk of recurrent ipsilateral ischemic stroke in patients with symptomatic near-occlusion with and without full collapse.Methods: Included were consecutive patients eligible for revascularization, grouped into symptomatic conventional ≥ 50% carotid stenosis (n = 266), near-occlusion without full collapse (n = 57) and near-occlusion with full collapse (n = 42). The risk of preoperative recurrent ipsilateral ischemic stroke was analyzed, or, for cases not revascularized within 90 days, 90-day risk was analyzed.Results: The risk of a preoperative recurrent ipsilateral ischemic stroke or ipsilateral retinal artery occlusion was 15% (95% CI 9–20%) for conventional ≥ 50% stenosis, 22% (95% CI 6–38%) among near-occlusion without full collapse and 30% (95% CI 16–44%) among near-occlusion with full collapse (p = 0.01, log rank test). In multivariate analysis, near-occlusion with full collapse had a higher risk of recurrent ipsilateral ischemic stroke (adjusted HR 2.6, 95% CI 1.3–5.3) and near-occlusion without full collapse tended to have a higher risk (adjusted HR 2.0, 95% CI 0.9–4.5) than conventional ≥ 50% stenosis. Only 24% of near-occlusion with full collapse underwent revascularization, common causes for abstaining were misdiagnosis as occlusion (31%), deemed surgically unfeasible (21%) and low perceived benefit (10%).Conclusions: Symptomatic carotid near-occlusion has a high short-term risk of recurrent ipsilateral ischemic stroke, especially near-occlusion with full collapse.
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| 4. |
- Haas, Brian J., et al.
(författare)
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De novo transcript sequence reconstruction from RNA-seq using the Trinity platform for reference generation and analysis
- 2013
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Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 8:8, s. 1494-1512
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Tidskriftsartikel (refereegranskat)abstract
- De novo assembly of RNA-seq data enables researchers to study transcriptomes without the need for a genome sequence; this approach can be usefully applied, for instance, in research on 'non-model organisms' of ecological and evolutionary importance, cancer samples or the microbiome. In this protocol we describe the use of the Trinity platform for de novo transcriptome assembly from RNA-seq data in non-model organisms. We also present Trinity-supported companion utilities for downstream applications, including RSEM for transcript abundance estimation, R/Bioconductor packages for identifying differentially expressed transcripts across samples and approaches to identify protein-coding genes. In the procedure, we provide a workflow for genome-independent transcriptome analysis leveraging the Trinity platform. The software, documentation and demonstrations are freely available from http://trinityrnaseq.sourceforge.net. The run time of this protocol is highly dependent on the size and complexity of data to be analyzed. The example data set analyzed in the procedure detailed herein can be processed in less than 5 h.
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| 5. |
- Johansson, Elias, et al.
(författare)
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Atherosclerotic ICA stenosis coinciding with ICA asymmetry associated with Circle of Willis variations can mimic near-occlusion
- 2020
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 62, s. 101-104
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Tidskriftsartikel (refereegranskat)abstract
- Differentiating carotid near-occlusion (tight atherosclerotic stenosis causing distal artery size reduction) from conventional stenosis is the first step when grading carotid stenoses with NASCET method. The internal carotid artery (ICA) can be asymmetrically associated with Circle of Willis variations. When such ICA asymmetry coincides with stenosis, it may mimic near-occlusion. We studied ICA anatomical variant prevalence in 4042 consecutive CTA exams from all indications, 53 excluded due to carotid occlusion, 814 with any >= 50% steno-occlusive disease intra- or extracranially, 3228 without. Of the 3989 included cases, 568 (14%) had ICA asymmetry, of which 335 (59%) were from associated with Circle of Willis variations. Of 3228 patients without >= 50% stenosis or other steno-occlusive disease intra- and extracranially; 257 (8.0%) demonstrated ICA asymmetry associated with Circle of Willis variations, equally common among sexes and age unrelated and most frequently attributed to an ipsilateral A1 hypoplasia/aplasia, less often attributed to large contralateral posterior communicating artery. As ICA asymmetry associated with Circle of Willis variations are common, caution should be exercised diagnosing near-occlusion on asymmetry alone.
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| 6. |
- Johansson, Elias, et al.
(författare)
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Carotid near-occlusion can be identified with ultrasound by low flow velocity distal to the stenosis
- 2019
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Ingår i: Acta Radiologica. - : Sage Publications. - 0284-1851 .- 1600-0455. ; 60:3, s. 396-404
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most carotid near-occlusions are indistinguishable from conventional >= 50% stenosis on ultrasound, demonstrating high peak systolic velocity (PSV) in the stenosis. Purpose To study whether the velocity distal to the stenosis can separate high PSV near-occlusion from conventional >= 50% stenosis.Material and Methods: We included patients with >= 50% carotid stenosis with high PSV (>= 125 cm/s), examined with both computed tomography angiography (CTA) and ultrasound within 30 days, and a distal velocity measurement was performed. Based on CTA, cases were divided into three groups: conventional stenosis; near-occlusion without full collapse (NwoC; normal-appearing albeit small distal artery); and near-occlusion with full collapse (NwC; threadlike distal artery). Distal Doppler ultrasound flow velocities were compared between these groups.Results: Sixty patients were included: 33 patients with conventional stenosis; 20 patients with NwoC; and seven patients with NwC. Mean distal PSV was 93, 63, and 21 cm/s (P < 0.001) and mean distal end-diastolic velocity was 30, 24, and 5 cm/s (P < 0.001), respectively. A distal PSV < 50 cm/s was 63% sensitive and 94% specific for separating both types of near-occlusion from conventional stenosis.Conclusion: In high PSV carotid stenoses, the distal velocity was lower in near-occlusions than conventional carotid stenosis. Distal velocities warrant further investigation in diagnostic studies.
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| 7. |
- Johansson, Elias, et al.
(författare)
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Carotid near-occlusion is often overlooked when CT angiography is assessed in routine practice
- 2020
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Ingår i: European Radiology. - : Springer. - 0938-7994 .- 1432-1084. ; 30:5, s. 2543-2551
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Assess the sensitivity and specificity of computed tomography angiography (CTA) for carotid near-occlusion diagnosis interpreted in clinical practice against expert assessment.Methods: CTAs were graded by two expert interpreters for near-occlusion. Findings were compared with clinical reports in 383 consecutive cases with symptomatic ≥ 50% carotid stenosis. In addition, 14 selected CTA exams (8 near-occlusions and 6 controls) were analyzed in a national effort by 13 radiologists experienced with carotid CTA.Results: In clinical practice, imaging reports were 20% (95% CI 12–28%) sensitive for near-occlusion, ranging 0–58% between different radiologists; specificity was 99%. Among the 13 radiologists reviewing the same 8 near-occlusions, the average sensitivity was 8%, ranging 0–75%; specificity was 100%.Conclusions: Carotid near-occlusion is systematically under-reported in clinical routine practice, caused by limited application of grading criteria when assessing CTA.
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| 8. |
- Johansson, Elias, et al.
(författare)
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Near-occlusion is difficult to diagnose with common carotid ultrasound methods
- 2021
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 63:5, s. 721-730
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To assess the sensitivity and specificity of common carotid ultrasound method for carotid near-occlusion diagnosis.Methods: Five hundred forty-eight patients examined with both ultrasound and CTA within 30 days of each other were analyzed. CTA graded by near-occlusion experts was used as reference standard. Low flow velocity, unusual findings, and commonly used flow velocity parameters were analyzed.Results: One hundred three near-occlusions, 272 conventional ≥50% stenosis, 162 <50% stenosis, and 11 occlusions were included. Carotid ultrasound was 22% (95%CI 14–30%; 23/103) sensitive and 99% (95%CI 99–100%; 442/445) specific for near-occlusion diagnosis. Near-occlusions overlooked on ultrasound were found misdiagnosed as occlusions (n = 13, 13%), conventional ≥50% stenosis (n = 65, 63%) and < 50% stenosis (n = 2, 2%). No velocity parameter or combination of parameters could identify the 65 near-occlusions mistaken for conventional ≥50% stenoses with >75% sensitivity and specificity.Conclusion: Near-occlusion is difficult to diagnose with commonly used carotid ultrasound methods. Improved carotid ultrasound methods are needed if ultrasound is to retain its position as sole preoperative modality.
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| 9. |
- Khangure, Simon R., et al.
(författare)
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Carotid near-occlusion frequently has high peak systolic velocity on Doppler ultrasound
- 2018
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Ingår i: Neuroradiology. - : Springer. - 0028-3940 .- 1432-1920. ; 60:1, s. 17-25
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Carotid near-occlusion is a tight atherosclerotic stenosis of the internal carotid artery (ICA) resulting in decrease in diameter of the vessel lumen distal to the stenosis. Near-occlusions can be classified as with or without full collapse, and may have high peak systolic velocity (PSV) across the stenosis, mimicking conventional > 50% carotid artery stenosis. We aimed to determine how frequently near-occlusions have high PSV in the stenosis and determine how accurately carotid Doppler ultrasound can distinguish high-velocity near-occlusion from conventional stenosis.Methods: Included patients had near-occlusion or conventional stenosis with carotid ultrasound and CT angiogram (CTA) performed within 30 days of each other. CTA examinations were analyzed by two blinded expert readers. Velocities in the internal and common carotid arteries were recorded. Mean velocity, pulsatility index, and ratios were calculated, giving 12 Doppler parameters for analysis.Results: Of 136 patients, 82 had conventional stenosis and 54 had near-occlusion on CTA. Of near-occlusions, 40 (74%) had high PSV (≥ 125 cm/s) across the stenosis. Ten Doppler parameters significantly differed between conventional stenosis and high-velocity near-occlusion groups. However, no parameter was highly sensitive and specific to separate the groups.Conclusion: Near-occlusions frequently have high PSV across the stenosis, particularly those without full collapse. Carotid Doppler ultrasound does not seem able to distinguish conventional stenosis from high-velocity near-occlusion. These findings question the use of ultrasound alone for preoperative imaging evaluation.
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| 10. |
- Ma, Li-Jun, et al.
(författare)
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Comparative genomics reveals mobile pathogenicity chromosomes in Fusarium.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 464:7287, s. 367-73
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Tidskriftsartikel (refereegranskat)abstract
- Fusarium species are among the most important phytopathogenic and toxigenic fungi. To understand the molecular underpinnings of pathogenicity in the genus Fusarium, we compared the genomes of three phenotypically diverse species: Fusarium graminearum, Fusarium verticillioides and Fusarium oxysporum f. sp. lycopersici. Our analysis revealed lineage-specific (LS) genomic regions in F. oxysporum that include four entire chromosomes and account for more than one-quarter of the genome. LS regions are rich in transposons and genes with distinct evolutionary profiles but related to pathogenicity, indicative of horizontal acquisition. Experimentally, we demonstrate the transfer of two LS chromosomes between strains of F. oxysporum, converting a non-pathogenic strain into a pathogen. Transfer of LS chromosomes between otherwise genetically isolated strains explains the polyphyletic origin of host specificity and the emergence of new pathogenic lineages in F. oxysporum. These findings put the evolution of fungal pathogenicity into a new perspective.
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