| 1. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 2. |
- Turtelboom,, et al.
(författare)
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The TESS-Keck Survey. XI. Mass Measurements for Four Transiting Sub-Neptunes Orbiting K Dwarf TOI-1246
- 2022
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 163:6
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Tidskriftsartikel (refereegranskat)abstract
- Multiplanet systems are valuable arenas for investigating exoplanet architectures and comparing planetary siblings. TOI-1246 is one such system, with a moderately bright K dwarf (V = 11.6, K = 9.9) and four transiting sub-Neptunes identified by TESS with orbital periods of 4.31, 5.90, 18.66, and 37.92 days. We collected 130 radial velocity observations with Keck/HIRES and TNG/HARPS-N to measure planet masses. We refit the 14 sectors of TESS photometry to refine planet radii (2.97 +/- 0.06 R (circle plus), 2.47 +/- 0.08 R (circle plus), 3.46 +/- 0.09 R (circle plus), and 3.72 +/- 0.16 R (circle plus)) and confirm the four planets. We find that TOI-1246 e is substantially more massive than the three inner planets (8.1 +/- 1.1 M (circle plus), 8.8 +/- 1.2 M (circle plus), 5.3 +/- 1.7 M (circle plus), and 14.8 +/- 2.3 M (circle plus)). The two outer planets, TOI-1246 d and TOI-1246 e, lie near to the 2:1 resonance (P (e)/P ( d ) = 2.03) and exhibit transit-timing variations. TOI-1246 is one of the brightest four-planet systems, making it amenable for continued observations. It is one of only five systems with measured masses and radii for all four transiting planets. The planet densities range from 0.70 +/- 0.24 to 3.21 +/- 0.44 g cm(-3), implying a range of bulk and atmospheric compositions. We also report a fifth planet candidate found in the RV data with a minimum mass of 25.6 +/- 3.6 M (circle plus). This planet candidate is exterior to TOI-1246 e, with a candidate period of 93.8 days, and we discuss the implications if it is confirmed to be planetary in nature.
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| 3. |
- Nik-Zainal, Serena, et al.
(författare)
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 534:7605, s. 47-54
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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.
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| 4. |
- Agyemang, Alex Adusei, et al.
(författare)
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Cell-free oxidized hemoglobin drives reactive oxygen species production and pro-inflammation in an immature primary rat mixed glial cell culture
- 2021
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Germinal matrix intraventricular hemorrhage (GM-IVH) is associated with deposition of redox active cell-free hemoglobin (Hb), derived from hemorrhagic cerebrospinal fluid (CSF), in the cerebrum and cerebellum. In a recent study, using a preterm rabbit pup model of IVH, intraventricularly administered haptoglobin (Hp), a cell-free Hb scavenger, partially reversed the damaging effects observed following IVH. Together, this suggests that cell-free Hb is central in the pathophysiology of the injury to the immature brain following GM-IVH. An increased understanding of the causal pathways and metabolites involved in eliciting the damaging response following hemorrhage is essential for the continued development and implementation of neuroprotective treatments of GM-IVH in preterm infant.METHODS: We exposed immature primary rat mixed glial cells to hemorrhagic CSF obtained from preterm human infants with IVH (containing a mixture of Hb-metabolites) or to a range of pure Hb-metabolites, incl. oxidized Hb (mainly metHb with iron in Fe3+), oxyHb (mainly Fe2+), or low equivalents of heme, with or without co-administration with human Hp (a mixture of isotype 2-2/2-1). Following exposure, cellular response, reactive oxygen species (ROS) generation, secretion and expression of pro-inflammatory cytokines and oxidative markers were evaluated.RESULTS: Exposure of the glial cells to hemorrhagic CSF as well as oxidized Hb, but not oxyHb, resulted in a significantly increased rate of ROS production that positively correlated with the rate of production of pro-inflammatory and oxidative markers. Congruently, exposure to oxidized Hb caused a disintegration of the polygonal cytoskeletal structure of the glial cells in addition to upregulation of F-actin proteins in microglial cells. Co-administration of Hp partially reversed the damaging response of hemorrhagic CSF and oxidized Hb.CONCLUSION: Exposure of mixed glial cells to oxidized Hb initiates a pro-inflammatory and oxidative response with cytoskeletal disintegration. Early administration of Hp, aiming to minimize the spontaneous autoxidation of cell-free oxyHb and liberation of heme, may provide a therapeutic benefit in preterm infant with GM-IVH.
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| 5. |
- Cochrane, Helen, et al.
(författare)
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Evidence-based practice in education for prosthetic orthotic occupations
- 2023
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Ingår i: ISPO 19th World Congress, 24-27 April 2023, Guadalajara, Mexico – Abstract book. - : Wolters Kluwer. ; , s. 48-48
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Konferensbidrag (refereegranskat)abstract
- This symposium aims to present the current state of evidence-based practice in education for prosthetic orthotic occupations. Presenters will share the current evidence, best practices and ongoing development of a research plan for prosthetic orthotic educators.The symposium will follow on from the Global Educators Meeting (GEM) in June 2022 the symposium will present the findings of the educator focus groups held during the GEM and discuss the educators survey.Presented by educators aimed at educators this symposium offers an opportunity to learn, contribute and discuss how to get the most out of educational time.The objective of this symposium are to help educators in prosthetic orthotic occupations;become more aware of the current evidence, best practices and the work currently ongoing to advance the evidence base for teaching in the field.cultivate collaborations among educator peers.develop and diversify educational practices to stimulate an effective learning environment.Statement of the objective/learning objectivesThe objectives of this symposium are to help educators in prosthetic orthotic occupations;become more aware of the current evidence, best practices and the evidence basecultivate collaborationsdevelop and diversify educational practices
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| 6. |
- Djoussé, Luc, et al.
(författare)
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Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
- 2004
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
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Tidskriftsartikel (refereegranskat)abstract
- Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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| 7. |
- Donker, Erik, et al.
(författare)
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European List of Essential Medicines for Medical Education : a protocol for a modified Delphi study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education. Methods and analysis This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in >= 80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision. Ethics and dissemination The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO-ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.
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| 8. |
- Donker, Erik M., et al.
(författare)
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The European List of Key Medicines for Medical Education: A Modified Delphi Study
- 2024
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Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 115:3, s. 515-524
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Tidskriftsartikel (refereegranskat)abstract
- Rational prescribing is essential for the quality of health care. However, many final-year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2-round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti-infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country-specific lists and could be used for the training and assessment of CPT.
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| 9. |
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| 10. |
- Goossens, Maria E., et al.
(författare)
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International pooled study on diet and bladder cancer : the bladder cancer, epidemiology and nutritional determinants (BLEND) study: design and baseline characteristics
- 2016
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Ingår i: Archives of Public Health. - : BMC. - 0778-7367 .- 2049-3258. ; 74
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2012, more than 400,000 urinary bladder cancer cases occurred worldwide, making it the 7th most common type of cancer. Although many previous studies focused on the relationship between diet and bladder cancer, the evidence related to specific food items or nutrients that could be involved in the development of bladder cancer remains inconclusive. Dietary components can either be, or be activated into, potential carcinogens through metabolism, or act to prevent carcinogen damage. Methods/design: The BLadder cancer, Epidemiology and Nutritional Determinants (BLEND) study was set up with the purpose of collecting individual patient data from observational studies on diet and bladder cancer. In total, data from 11,261 bladder cancer cases and 675,532 non-cases from 18 case-control and 6 cohort studies from all over the world were included with the aim to investigate the association between individual food items, nutrients and dietary patterns and risk of developing bladder cancer. Discussion: The substantial number of cases included in this study will enable us to provide evidence with large statistical power, for dietary recommendations on the prevention of bladder cancer.
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