| 1. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 2. |
- Buitelaar, Jan K, et al.
(författare)
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A comparison of North American versus non-North American ADHD study populations.
- 2006
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Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 15:3, s. 177-181
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Tidskriftsartikel (refereegranskat)abstract
- Few large, prospective clinical studies in Europe have assessed the validity and applicability of research methods used to study ADHD in North America. To assess comparability of study populations, we examined baseline patient characteristics from a group of North American studies against those of a large European/African/Australian study. All studies used identical diagnostic assessments and inclusion criteria, with ADHD diagnosis and the presence of comorbid psychiatric conditions confirmed using the KSADS-PL. Raters were trained and assessed to ensure uniform diagnostic and symptom severity rating standards. Six hundred and four patients (mean age = 10.2 years) enrolled in the non-North American study, and 665 patients (mean age = 10.4 years) enrolled in the North American study. The proportion of girls was higher in the North American studies (29.2% vs. 10.4%, p < 0.001). In both groups, most patients had a positive family history of ADHD and previous stimulant treatment. Fewer had the inattentive subtype of ADHD, and mean severity was slightly higher in the non-North American study. Results demonstrate that, when a uniform set of rigorous, standardized diagnostic criteria are used by skilled clinicians, the patient populations identified are generally similar. This supports the practice of generalizing results from treatment studies across geographies.
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| 3. |
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| 4. |
- Hazell, P, et al.
(författare)
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Presence and abundance of four epiphytic bryophytes in relation to density of aspen (Populus tremula) and other stand characteristics
- 1998
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Ingår i: Forest Ecology and Management. - 0378-1127 .- 1872-7042. ; 107:1-3, s. 147-158
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Tidskriftsartikel (refereegranskat)abstract
- The influence of the local density of aspen on the presence and abundance of four epiphytic bryophytes was investigated in four mixed forest stands in Central Sweden, each about 30 ha and aged 70-120 yr. Cover of the bryophytes Nyholmiella obtusifolia, Orthotrichum speciosum, Pylaisia polyantha and Radula complanata (the four most frequent aspen-specific epiphytic bryophytes in this region) was recorded on the bark of 155 systematically sampled aspen stems. In circular plots with 10 m radius surrounding each sampled aspen, information on ground vegetation, soil moisture and stand density was collected. In these plots, and also in plots with 5 m and 20 m radius, stem number and diameters of aspen trees were recorded together with an observation of the presence/absence of the four bryophytes. There was no general and consistent relation between aspen density and presence or abundance of the studied bryophytes. Site, host aspen diameter and forest stand structures were more important for the bryophytes. The site factor explained more of the variation than any of the studied variables. All species except N. obtusifolia were favoured by a large diameter of the host tree, and the density of the surrounding forest stand had a positive effect on the cover of Pyl. polyantha and R. complanata. The practical implications of the results are discussed.
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| 5. |
- Miller, Norman E., et al.
(författare)
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Secretion of adipokines by human adipose tissue in vivo : partitioning between capillary and lymphatic transport
- 2011
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, Md. : American Physiological Society. - 0193-1849 .- 1522-1555. ; 301:4, s. E659-E667
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Tidskriftsartikel (refereegranskat)abstract
- Peptides secreted by adipose tissue (adipokines) may enter blood via capillaries or lymph. The relative importance of these pathways for a given adipokine might influence its biological effects. Because this has not been studied in any species, we measured the concentrations of seven adipokines and eight nonsecreted proteins in afferent peripheral lymph and venous plasma from 12 healthy men. Data for nonsecreted proteins were used to derive indices of microvascular permeability, which in conjunction with the molecular radii of the adipokines were used to estimate the amounts leaving the tissue via capillaries. Transport rates via lymph were estimated from the lymph adipokine concentrations and lymph flow rates and total transport (secretion) as the sum of this and capillary transport. Concentrations of nonsecreted proteins were always lower in lymph than in plasma. With the exception of adiponectin, adipokine concentrations were always higher in lymph (P < 0.01). Leptin and MCP-1 were secreted at the highest rates (means: 43 mu g/h or 2.7 nmol/h and 32 mu g/h or 2.4 nmol/h, respectively). IL-6 and MCP-1 secretion rates varied greatly between subjects. The proportion of an adipokine transported via lymph was directly related to its molecular radius (r(s) = +0.94, P = 0.025, n = 6), increasing from 14 to 100% as the radius increased from 1.18 (IL-8) to 3.24 nm (TNF alpha). We conclude that the lymph/capillary partitioning of adipokines is a function of molecular size, which may affect both their regional and systemic effects in vivo. This finding may have implications for the physiology of peptides secreted by other tissues.
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