| 1. |
- Komatsu, Kimberly J., et al.
(författare)
-
Global change effects on plant communities are magnified by time and the number of global change factors imposed
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:36, s. 17867-17873
-
Tidskriftsartikel (refereegranskat)abstract
- Accurate prediction of community responses to global change drivers (GCDs) is critical given the effects of biodiversity on ecosystem services. There is consensus that human activities are driving species extinctions at the global scale, but debate remains over whether GCDs are systematically altering local communities worldwide. Across 105 experiments that included over 400 experimental manipulations, we found evidence for a lagged response of herbaceous plant communities to GCDs caused by shifts in the identities and relative abundances of species, often without a corresponding difference in species richness. These results provide evidence that community responses are pervasive across a wide variety of GCDs on long-term temporal scales and that these responses increase in strength when multiple GCDs are simultaneously imposed.Global change drivers (GCDs) are expected to alter community structure and consequently, the services that ecosystems provide. Yet, few experimental investigations have examined effects of GCDs on plant community structure across multiple ecosystem types, and those that do exist present conflicting patterns. In an unprecedented global synthesis of over 100 experiments that manipulated factors linked to GCDs, we show that herbaceous plant community responses depend on experimental manipulation length and number of factors manipulated. We found that plant communities are fairly resistant to experimentally manipulated GCDs in the short term (<10 y). In contrast, long-term (≥10 y) experiments show increasing community divergence of treatments from control conditions. Surprisingly, these community responses occurred with similar frequency across the GCD types manipulated in our database. However, community responses were more common when 3 or more GCDs were simultaneously manipulated, suggesting the emergence of additive or synergistic effects of multiple drivers, particularly over long time periods. In half of the cases, GCD manipulations caused a difference in community composition without a corresponding species richness difference, indicating that species reordering or replacement is an important mechanism of community responses to GCDs and should be given greater consideration when examining consequences of GCDs for the biodiversity–ecosystem function relationship. Human activities are currently driving unparalleled global changes worldwide. Our analyses provide the most comprehensive evidence to date that these human activities may have widespread impacts on plant community composition globally, which will increase in frequency over time and be greater in areas where communities face multiple GCDs simultaneously.
|
|
| 2. |
- Nik-Zainal, Serena, et al.
(författare)
-
Mutational Processes Molding the Genomes of 21 Breast Cancers
- 2012
-
Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 149:5, s. 979-993
-
Tidskriftsartikel (refereegranskat)abstract
- All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
|
|
| 3. |
- Hillier, Ladeana W, et al.
(författare)
-
Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution
- 2004
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 432:7018, s. 695-716
-
Tidskriftsartikel (refereegranskat)abstract
- We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.
|
|
| 4. |
- Nik-Zainal, Serena, et al.
(författare)
-
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
-
Tidskriftsartikel (refereegranskat)abstract
- We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
|
|
| 5. |
- Glasbey, JC, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
|
|
| 7. |
- Basu, Neil, et al.
(författare)
-
EULAR points to consider in the development of classification and diagnostic criteria in systemic vasculitis
- 2010
-
Ingår i: Annals of the Rheumatic Diseases. - London, UK : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1744-1750
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The systemic vasculitides are multiorgan diseases where early diagnosis and treatment can significantly improve outcomes. Robust nomenclature reduces diagnostic delay. However, key aspects of current nomenclature are widely perceived to be out of date, these include disease definitions, classification and diagnostic criteria. Therefore, the aim of the present work was to identify deficiencies and provide contemporary points to consider for the development of future definitions and criteria in systemic vasculitis. Methods The expert panel identified areas of concern within existing definitions/criteria. Consequently, a systematic literature review was undertaken looking to address these deficiencies and produce 'points to consider' in accordance with standardised European League Against Rheumatism (EULAR) operating procedures. In the absence of evidence, expert consensus was used. Results There was unanimous consensus for re-evaluating existing definitions and developing new criteria. A total of 17 points to consider were proposed, covering 6 main areas: biopsy, laboratory testing, diagnostic radiology, nosology, definitions and research agenda. Suggestions to improve and expand current definitions were described including the incorporation of anti-neutrophil cytoplasm antibody and aetiological factors, where known. The importance of biopsy in diagnosis and exclusion of mimics was highlighted, while equally emphasising its problems. Thus, the role of alternative diagnostic tools such as MRI, ultrasound and surrogate markers were also discussed. Finally, structures to develop future criteria were considered. Conclusions Limitations in current classification criteria and definitions for vasculitis have been identified and suggestions provided for improvement. Additionally it is proposed that, in combination with the updated evidence, these should form the basis of future attempts to develop and validate revised criteria and definitions of vasculitis.
|
|
| 8. |
|
|
| 9. |
- Herrick, Ariane L, et al.
(författare)
-
Treatment outcome in early diffuse cutaneous systemic sclerosis : The European Scleroderma Observational Study (ESOS)
- 2017
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 76:7, s. 1207-1218
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Results Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed.
|
|
| 10. |
- Iliodromiti, Stamatina, et al.
(författare)
-
Liver, visceral and subcutaneous fat in men and women of South Asian and white European descent : a systematic review and meta-analysis of new and published data
- 2023
-
Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:1, s. 44-56
-
Forskningsöversikt (refereegranskat)abstract
- Aims/hypothesis South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. Methods We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries (https://osf. io/w5bf9). Results We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m(2) lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I-2 =83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I-2 =93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19;1 2 =85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m(2) lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I-2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I-2 =72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I-2 =71%) did not differ significantly between ethnic groups in eight studies of women. Conclusions/interpretation South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians.
|
|
