| 1. |
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| 2. |
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Overview of the JET results
- 2015
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Tidskriftsartikel (refereegranskat)
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| 3. |
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| 4. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 5. |
- Leebens-Mack, James H., et al.
(författare)
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One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
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Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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| 6. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 7. |
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| 8. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 9. |
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| 10. |
- Wahl, Simone, et al.
(författare)
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Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
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| 11. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 12. |
- Fisher, Matthew C., et al.
(författare)
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Development and worldwide use of non-lethal, and minimal population-level impact, protocols for the isolation of amphibian chytrid fungi
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Parasitic chytrid fungi have emerged as a significant threat to amphibian species worldwide, necessitating the development of techniques to isolate these pathogens into culture for research purposes. However, early methods of isolating chytrids from their hosts relied on killing amphibians. We modified a pre-existing protocol for isolating chytrids from infected animals to use toe clips and biopsies from toe webbing rather than euthanizing hosts, and distributed the protocol to researchers as part of the BiodivERsA project RACE; here called the RML protocol. In tandem, we developed a lethal procedure for isolating chytrids from tadpole mouthparts. Reviewing a database of use a decade after their inception, we find that these methods have been applied across 5 continents, 23 countries and in 62 amphibian species. Isolation of chytrids by the non-lethal RML protocol occured in 18% of attempts with 207 fungal isolates and three species of chytrid being recovered. Isolation of chytrids from tadpoles occured in 43% of attempts with 334 fungal isolates of one species (Batrachochytrium dendrobatidis) being recovered. Together, these methods have resulted in a significant reduction and refinement of our use of threatened amphibian species and have improved our ability to work with this group of emerging pathogens.
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| 13. |
- Goddek, S., et al.
(författare)
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Nutrient mineralization and organic matter reduction performance of RAS-based sludge in sequential UASB-EGSB reactors
- 2018
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Ingår i: Aquacultural Engineering. - : Elsevier BV. - 0144-8609 .- 1873-5614. ; 83, s. 10-19
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Tidskriftsartikel (refereegranskat)abstract
- There is a recognized need for mineralizing aquaculture-derived sludge in aquaponics systems in order to reduce waste production. Many recent studies of aquacultural waste treatment have focused only the production of biogas as opposed to the potential for mineralization of nutrient-rich sludge. Upflow anaerobic sludge blanket (UASB) reactors provide one possible solution for breaking down sludge into bioavailable nutrients that can subsequently be delivered to plants. As such, this study examines the mineralization performance of sequential UASB reactors that are designed with an expanded granular sludge bed (EGSB) and compared to standard aerobic and anaerobic batch reactors. Results of our experiments demonstrate that only chemical oxygen demand reduction is significantly different. An unexpected drop in pH of one of the three reactor systems revealed that a pH below 6 was able to significantly increase the mineralization and mobilization of nutrients. Approximately 25% of phosphorus, potassium, and calcium could also be recovered from the sludge under lower pH conditions, as compared to the mineralization performance of standard UASB reactors running at a higher pH. However, the opposite effect was observed with respect to organic sludge reduction, where diminished performance was observed in the low-pH reactor. The current study implies that anaerobic reactors operating at low pH can potentially contribute towards improved nutrient recovery in multi-loop aquaponics systems and reduction of additive agents for pH control of the hydroponic subsystem. © 2018 Elsevier B.V.
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| 14. |
- Martinez-Ramirez, Daniel, et al.
(författare)
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Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome : The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry
- 2018
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 75:3, s. 353-359
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).MAIN OUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events.RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P<.001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P <.001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P <.001). The overall adverse event rate was 35.4%(56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).CONCLUSIONS AND RELEVANCE Deep brain stimulationwas associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.
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| 15. |
- Smith, Gustav, et al.
(författare)
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Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
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| 16. |
- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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| 17. |
- Bainomugisha, Engineer, et al.
(författare)
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Message from Chairs of SEiA 2018
- 2018
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Ingår i: Proceedings - International Conference on Software Engineering. - New York, NY, USA : ACM. - 0270-5257. ; 2018, s. x-xi
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Concepcion Gil-Rodriguez, Maria, et al.
(författare)
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De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes
- 2015
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Ingår i: Human Mutation. - : Wiley: 12 months. - 1059-7794 .- 1098-1004. ; 36:4, s. 454-462
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for approximate to 1%-2% of CdLS-like phenotypes.
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| 19. |
- Dudding, Tom, et al.
(författare)
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Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.
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| 20. |
- Genshaft, Alex S., et al.
(författare)
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Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction
- 2016
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- We present a scalable, integrated strategy for coupled protein and RNA detection from single cells. Our approach leverages the DNA polymerase activity of reverse transcriptase to simultaneously perform proximity extension assays and complementary DNA synthesis in the same reaction. Using the Fluidigm C1 (TM) system, we profile the transcriptomic and proteomic response of a human breast adenocarcinoma cell line to a chemical perturbation, benchmarking against in situ hybridizations and immunofluorescence staining, as well as recombinant proteins, ERCC Spike-Ins, and population lysate dilutions. Through supervised and unsupervised analyses, we demonstrate synergies enabled by simultaneous measurement of single-cell protein and RNA abundances. Collectively, our generalizable approach highlights the potential for molecular metadata to inform highly-multiplexed single-cell analyses.
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| 21. |
- Goncalves-Pereira, M, et al.
(författare)
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[Needs for Care and Service Use in Dementia: Baseline Assessment of Portuguese Participants in the Actifcare Cohort Study]
- 2019
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Ingår i: Acta medica portuguesa. - : Ordem dos Medicos. - 1646-0758 .- 0870-399X. ; 32:5, s. 355-367
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Tidskriftsartikel (refereegranskat)abstract
- Introdução: As pessoas com demência e os seus familiares deveriam ter acesso atempado a cuidados formais na comunidade (centros de dia, apoio domiciliário). O projecto EU-Actifcare investigou o acesso/utilização destes serviços em países europeus. Descrevemos a implementação do estudo de coorte e a avaliação inicial em Portugal, com foco nas necessidades de cuidados e recurso aos serviços.Material e Métodos: Selecionámos uma amostra de conveniência de 66 pessoas com diagnóstico de demência ligeira a moderada (residindo na comunidade sem cuidados formais relevantes) e respetivos familiares-cuidadores. A avaliação (clínico-funcional e social) incluiu os instrumentos Camberwell Assessment of Need for the Elderly e Resource Utilization in Dementia.Resultados: Identificámos necessidades não-cobertas dos doentes (média 1,1; DP = 1,7), principalmente de companhia (23% dos casos), sofrimento psicológico (20%) e atividades diárias (14%). Os familiares-cuidadores dedicavam 150 minutos/dia (mediana) à prestação de cuidados e 44% apresentavam necessidades não-cobertas de sofrimento psicológico. Quando havia problemas de acesso/utilização dos serviços de saúde e sociais na comunidade, estes estavam frequentemente relacionados com recusa ou desconhecimento de utentes/familiares.Discussão: A seleção dos participantes não foi fácil, pela especificidade dos critérios adotados. Não almejando representatividade nacional, recrutámos uma amostra típica de pessoas em estádios ligeiros a moderados de demência, em serviços e regiões diferentes. Nalguns casos, encontrámos necessidades não-cobertas e repercussões familiares que já justificariam respostas de serviços na comunidade, não fossem os problemas de acesso/utilização.Conclusão: Na área das demências, existem dificuldades no acesso atempado e utilização efectiva de cuidados formais, coexistindo com uma cobertura menor de necessidades específicas.
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| 22. |
- Joyce, Alyssa, et al.
(författare)
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The role of exopolymers in hatcheries: an overlooked factor in hatchery hygiene and feed quality
- 2015
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Ingår i: Aquaculture. - : Elsevier BV. - 0044-8486. ; 446, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular Polymeric Substances (EPS),(1) or exopolymers, play vital roles in the productivity of commercial hatcheries, yet have received little attention in aquaculture outside of their role in the biofilters of recirculating systems. Hatcheries have long dealt with EPS in microalgal cultures or larval rearing systems when quantities manifest themselves visually as biofilms or mucilaginous aggregates. The same polymers in lesser, visually undetectable quantities have the ability to attract commensal bacteria and sequester micronutrients, which can be essential in hatcheries for hygiene, stability of rearing environments, and the production of microalgae for live feeds. EPS may also serve an important role in nutrition both directly in the particle selection of filter feeders, and indirectly through their contribution to microflora in the larval gut of both fish and invertebrates. EPS have been well-studied in marine ecosystems, but their presence in hatcheries has until recently been largely overlooked, perhaps on account of their invisibility using normal microscopy and their extremely small size, both factors which may explain why they are sometimes also referred to as transparent exopolymeric substances (TEPs). This review examines recent literature for ways in which EPS affect hatchery processes, with suggestions as to how further research and development of biosensor technologies for EPS have the potential to improve production processes. (C) 2015 The Authors. Published by Elsevier B.V.
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| 23. |
- Joyce, Alyssa, et al.
(författare)
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Toward Selective Breeding of a Hermaphroditic Oyster Ostrea chilensis: Roles of Nutrition and Temperature in Improving Fecundity and Synchrony of Gamete Release
- 2015
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Ingår i: Journal of Shellfish Research. - : National Shellfisheries Association. - 0730-8000 .- 1943-6319. ; 34:3, s. 831-840
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Tidskriftsartikel (refereegranskat)abstract
- Physiological characteristics of gametogenesis, fertilization, and early larval development in Ostrea chilensis (Philippi, 1845) pose a number of challenges for selective breeding, despite strong commercial potential. In wild populations, this larviparous protandric hermaphrodite exhibits asynchronous gonadal maturation and relatively low fecundity. Reproductive success and genetic diversity in a hatchery population are primarily determined by female fecundity and fertility, as well as synchrony of female gonad development. Better hatchery control of the reproductive cycle can lead to more cost-effective and reliable breeding. This study examined factors such as feed and temperature in an attempt to increase reproductive rates and female sex ratios in brood stock. Oysters held under two different hatchery conditioning regimes-flow-through outdoor nursery ponds and temperature-controlled indoor tanks-spawned earlier and had higher reproductive rates than natural or farmed populations. Oysters were sampled over 6 months with histological analysis used to assess seasonal gamete patterns. Magnetic resonance imaging was also trialed and compared with histology findings. Significant increase in female gonad proportion and improved synchrony of egg maturation was observed through manipulation of feed and temperature. The implications of these findings for implementing a cost-effective selective breeding program in this species are outlined.
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| 24. |
- Joyce, W., et al.
(författare)
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Adrenergic and adenosinergic regulation of the cardiovascular system in an Antarctic icefish: Insight into central and peripheral determinants of cardiac output
- 2019
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Ingår i: Comparative Biochemistry and Physiology a-Molecular & Integrative Physiology. - : Elsevier BV. - 1095-6433. ; 230, s. 28-38
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Tidskriftsartikel (refereegranskat)abstract
- Icefishes characteristically lack the oxygen-binding protein haemoglobin and therefore are especially reliant on cardiovascular regulation to augment oxygen transport when oxygen demand increases, such as during activity and warming. Using both in vivo and in vitro experiments, we evaluated the roles for adrenaline and adenosine, two well-established cardio- and vasoactive molecules, in regulating the cardiovascular system of the blackfin icefish, Chaenocephalus aceratus. Despite increasing cardiac contractility (increasing twitch force and contraction kinetics in isometric myocardial strip preparations) and accelerating heart rate (f(H)), adrenaline (5 nmol kg(-1) bolus infra-arterial injection) did not significantly increase cardiac output ((Q) over dot) in vivo because it elicited a large decrease in vascular conductance (G(sys)). In contrast, and despite preliminary data suggesting a direct negative inotropic effect of adenosine on isolated atria and little effect on isolated ventricle strips, adenosine (500 nmol kg-1) generated a large increase in (Q) over dot by increasing G(sys), a change reminiscent of that previously reported during both acute warming and invoked activity. Our data thus illustrate how (Q) over dot in C. aceratus may be much more dependent on peripheral control of vasomotor tone than direct regulation of the heart.
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| 25. |
- Joyce, W., et al.
(författare)
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Exploring nature's natural knockouts: in vivo cardiorespiratory performance of Antarctic fishes during acute warming
- 2018
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 221:15
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Tidskriftsartikel (refereegranskat)abstract
- We tested the hypothesis that blackfin icefish (Chaenocephalus aceratus), one of the six species in the family Channichthyidae (the icefishes) that do not express haemoglobin and myoglobin, lack regulatory cardiovascular flexibility during acute warming and activity. The experimental protocols were designed to optimize the surgical protocol and minimize stress. First, minimally invasive heart rate (f(H)) measurements were made during a thermal ramp until cardiac failure in C. aceratus and compared with those from the closely related red-blooded black rockcod (Notothenia coriiceps). Then, integrative cardiovascular adjustments were more extensively studied using flow probes and intravascular catheters in C. aceratus during acute warming (from 0 to 8 degrees C) at rest and after imposed activity. Chaenocephalus aceratus had a lower routine f H than N. coriiceps (9 beats min(-1) versus 14 beats min(-1)) and a lower peak f(H )during acute warming (38 beats min' versus 55 beats min(-1)) with a similar cardiac breakpoint temperature (13 and 14 degrees C, respectively). Routine cardiac output ((Q) over dot) for C. aceratus at similar to 0 degrees C was much lower (26.6 ml min(-1) kg(-1)) than previously reported, probably because fish in the present study had a low f(H) (12 beats min(-1)) indicative of a high routine vagal tone and low stress. Chaenocephalus aceratus increased oxygen consumption during acute warming and with activity. Correspondingly, (Q) over dot increased considerably (maximally 86.3 ml min(-1) kg(-1)), as did vascular conductance (5-fold). Thus, unlike earlier suggestions, these data provide convincing evidence that icefish can mount a well-developed cardiovascular regulation of heart rate, cardiac output and vascular conductance, and this regulatory capacity provides flexibility during acute warming.
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| 26. |
- Joyce, W., et al.
(författare)
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The effects of thermal acclimation on cardio-respiratory performance in an Antarctic fish (Notothenia coriiceps)
- 2018
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Ingår i: Conservation Physiology. - : Oxford University Press (OUP). - 2051-1434. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean has experienced stable, cold temperatures for over 10 million years, yet particular regions are currently undergoing rapid warming. To investigate the impacts of warming on cardiovascular oxygen transport, we compared the cardio-respiratory performance in an Antarctic notothenioid (Notothenia coriiceps) that was maintained at 0 or 5 degrees C for 6.0-9.5 weeks. When compared at the fish's respective acclimation temperature, the oxygen consumption rate and cardiac output were significantly higher in 5 degrees C-acclimated than 0 degrees C-acclimated fish. The 2.7-fold elevation in cardiac output in 5 degrees C-acclimated fish (17.4 vs. 6.5 ml min(-1) kg(-1)) was predominantly due to a doubling of stroke volume, likely in response to increased cardiac preload, as measured by higher central venous pressure (0.15 vs. 0.08 kPa); tachycardia was minor (295 vs. 25.2 beats min(-1)). When fish were acutely warmed, oxygen consumption rate increased by similar amounts in 0 degrees C- and 5 degrees C-acclimated fish at equivalent test temperatures. In both acclimation groups, the increases in oxygen consumption rate during acute heating were supported by increased cardiac output achieved by elevating heart rate, while stroke volume changed relatively little. Cardiac output was similar between both acclimation groups until 12 degrees C when cardiac output became significantly higher in 5 degrees C-acclimated fish, driven largely by their higher stroke volume. Although cardiac arrhythmias developed at a similar temperature (similar to 14.5 degrees C) in both acclimation groups, the hearts of 5 degrees C-acclimated fish continued to pump until significantly higher temperatures (CTmax for cardiac function 17.7 vs. 15.0 degrees C for 0 degrees C-acclimated fish). These results demonstrate that N. coriiceps is capable of increasing routine cardiac output during both acute and chronic warming, although the mechanisms are different (heart rate-dependent versus primarily stroke volume-dependent regulation, respectively). Cardiac performance was enhanced at higher temperatures following 5 degrees C acclimation, suggesting cardiovascular function may not constrain the capacity of N. coriiceps to withstand a warming climate.
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| 27. |
- Klünder, Jil, et al.
(författare)
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Catching up with Method and Process Practice: An Industry-Informed Baseline for Researchers
- 2019
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Ingår i: Proceedings - 2019 IEEE/ACM 41st International Conference on Software Engineering: Software Engineering in Practice, ICSE-SEIP 2019. ; May 2019, s. 255-264
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Konferensbidrag (refereegranskat)abstract
- Software development methods are usually not applied by the book.companies are under pressure to continuously deploy software products that meet market needs and stakeholders' requests. To implement efficient and effective development processes, companies utilize multiple frameworks, methods and practices, and combine these into hybrid methods. A common combination contains a rich management framework to organize and steer projects complemented with a number of smaller practices providing the development teams with tools to complete their tasks. In this paper, based on 732 data points collected through an international survey, we study the software development process use in practice. Our results show that 76.8% of the companies implement hybrid methods.company size as well as the strategy in devising and evolving hybrid methods affect the suitability of the chosen process to reach company or project goals. Our findings show that companies that combine planned improvement programs with process evolution can increase their process' suitability by up to 5%.
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| 28. |
- Lunetta, Kathryn L., et al.
(författare)
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Rare coding variants and X-linked loci associated with age at menarche
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only similar to 3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency proteincoding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P<5 x 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P = 9.4 x 10(-13)) and FAAH2 (rs5914101, P = 4.9 x 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P = 2.8 x 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain similar to 0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
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| 29. |
- Moreno, Silvia Suñer
(författare)
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Investigation of Carbon Reinforced UHMWPE Nanocomposites for use in Orthopaedics
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Over the lifetime of a person, the function of the natural hip joint can be altered due to trauma or disease and an artificial hip replacement may eventually be required. Ultra high molecular weight polyethylene (UHMWPE) is considered the gold standard material for the acetabular cup in hip arthroplasties. However, problems associated with the release of UHMWPE wear particles, due to the relative motion between the bearing components, can lead to the eventual failure of the implant. The first part of this thesis focuses on reviewing the current status of total joint replacement research, with particular attention to implant bearing materials, implant wear particles and biological responses to wear particles. Subsequently, the thesis focuses on the potential of UHMWPE-based nanocomposites as an alternative to UHMWPE. A suitable method to prepare carbon nanoparticle reinforced UHMWPE materials was developed, and the possibilities of multi-walled carbon nanotubes (MWCNTs) and graphene oxide (GO) as reinforcements of UHMWPE were investigated.The results of this thesis showed that, under optimised conditions, carbonnanoparticles have the ability to improve the overall performance of UHMWPE,without adversely affecting the biocompatibility. However, further investigations into appropriate GO and MWCNT surface modification methods are necessary to enhance the filler/matrix interaction and further improve the performance of the resulting nanocomposites. This thesis has provided an insight into the potential of UHMWPE-based nanocomposites as an alternative to UHMWPE for use in total joint replacements and further work concerning biological and mechanical characterisation has been suggested in order to fully understand the behaviour of these nanocomposites.
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| 30. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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| 31. |
- Parmar, Priyanka, et al.
(författare)
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Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults
- 2018
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 38, s. 206-216
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Tidskriftsartikel (refereegranskat)abstract
- Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0.012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 x 10(-7) < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 10(-8) < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. Fund: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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| 32. |
- Schilcher, Jörg, et al.
(författare)
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Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in Sweden: A Cross-Sectional Study
- 2015
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Ingår i: Journal of Bone and Mineral Research. - : WILEY-BLACKWELL. - 0884-0431 .- 1523-4681. ; 30:11, s. 2127-2132
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Tidskriftsartikel (refereegranskat)abstract
- We have previously noted a dichotomy in the location of atypical fractures along the femoral shaft in Swedish patients, and a mainly subtrochanteric location of atypical fractures in descriptions of patients from Singapore. These unexpected differences were now investigated by testing the following hypotheses in a cross-sectional study: first, that there is a dichotomy also in Singapore; second, that the relation between subtrochanteric and diaphyseal location is different between the two countries; third, that the location is related to femoral bow. The previously published Swedish sample (n = 151) was re-measured, and a new Singaporean sample (n = 75) was established. Both samples were based on radiographic classification of all femoral fractures in women above 55 years of age. The distance between the fracture line and the lesser trochanter was measured. Femoral bow was classified as present or absent on frontal radiographs. Frequency distribution of the measured distances was analyzed using the Bayesian information criterion to choose the best description of the observed variable distribution in terms of a compilation of normally distributed subgroups. The analysis showed a clear dichotomy of the fracture location: either subtrochanteric or diaphyseal. Subtrochanteric fractures comprised 48% of all fractures in Singapore, and 17% in Sweden (p = 0.0001). In Singapore, femoral bow was associated with more fractures in the diaphyseal subgroup (p = 0.0001). This was not seen in Sweden. A dichotomous location of atypical fractures was confirmed, because it was found also in Singapore. The fractures showed a different localization pattern in the two countries. This difference may be linked to anatomical variations, but might also be related to cultural differences between the two populations that influence physical activity. (c) 2015 American Society for Bone and Mineral Research
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| 33. |
- Walz, Ariane, et al.
(författare)
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Sociocultural valuation of ecosystem services for operational ecosystem management : mapping applications by decision contexts in Europe
- 2019
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Ingår i: Regional Environmental Change. - : Springer Science and Business Media LLC. - 1436-3798 .- 1436-378X. ; 19:8, s. 2245-2259
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Tidskriftsartikel (refereegranskat)abstract
- Sociocultural valuation (SCV) of ecosystem services (ES) discloses the principles, importance or preferences expressed by people towards nature. Although ES research has increasingly addressed sociocultural values in past years, little effort has been made to systematically review the components of sociocultural valuation applications for different decision contexts (i.e. awareness raising, accounting, priority setting, litigation and instrument design). In this analysis, we investigate the characteristics of 48 different sociocultural valuation applications—characterised by unique combinations of decision context, methods, data collection formats and participants—across ten European case studies. Our findings show that raising awareness for the sociocultural value of ES by capturing people’s perspective and establishing the status quo, was found the most frequent decision context in case studies, followed by priority setting and instrument development. Accounting and litigation issues were not addressed in any of the applications. We reveal that applications for particular decision contexts are methodologically similar, and that decision contexts determine the choice of methods, data collection formats and participants involved. Therefore, we conclude that understanding the decision context is a critical first step to designing and carrying out fit-for-purpose sociocultural valuation of ES in operational ecosystem management.
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