| 1. |
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 4. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 6. |
- Dunham, I, et al.
(författare)
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The DNA sequence of human chromosome 22
- 1999
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
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Tidskriftsartikel (refereegranskat)
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| 7. |
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| 8. |
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| 9. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 10. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 11. |
- 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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| 12. |
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| 13. |
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| 14. |
- O'Hanlon, Simon J., et al.
(författare)
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Recent Asian origin of chytrid fungi causing global amphibian declines
- 2018
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 360:6389, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of themost devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.
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| 15. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 16. |
- Omrani, A., et al.
(författare)
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Identification of Novel Neurocircuitry Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce Food Reward Seeking
- 2021
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 90:12, s. 843-852
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Leptin reduces the motivation to obtain food by modulating activity of the mesolimbic dopamine (DA) system upon presentation of cues that predict a food reward. Although leptin directly reduces the activity of ventral tegmental area (VTA) DA neurons, the majority of leptin receptor (LepR)-expressing DA neurons do not project to the nucleus accumbens, the projection implicated in driving food reward seeking. Therefore, the precise locus of leptin action to modulate motivation for a food reward is unresolved. METHODS: We used transgenic mice expressing Cre recombinase under the control of the LepR promoter, anatomical tracing, optogenetics-assisted patch-clamp electrophysiology, in vivo optogenetics with fiber photometric calcium measurements, and chemogenetics to unravel how leptin-targeted neurocircuitry inhibits food reward seeking. RESULTS: A large number of DA neurons projecting to the nucleus accumbens are innervated by local VTA LepR-expressing GABA (gamma-aminobutyric acid) neurons. Leptin enhances the activity of these GABA neurons and thereby inhibits nucleus accumbens-projecting DA neurons. In addition, we find that lateral hypothalamic LepR-expressing neurons projecting to the VTA are inhibited by leptin and that these neurons modulate DA neurons indirectly via inhibition of VTA GABA neurons. In accordance with such a disinhibitory function, optogenetically stimulating lateral hypothalamic LepR projections to the VTA potently activates DA neurons in vivo. Moreover, we found that chemogenetic activation of lateral hypothalamic LepR neurons increases the motivation to obtain a food reward only when mice are in a positive energy balance. CONCLUSIONS: We identify neurocircuitry through which leptin targets multiple inputs to the DA system to reduce food reward seeking.
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| 17. |
- Siles, Rogelio, et al.
(författare)
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Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents
- 2008
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 71:3, s. 313-320
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Tidskriftsartikel (refereegranskat)abstract
- Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI(50) = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC50 = 2.8 mu M). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.
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| 18. |
- Garner, J., et al.
(författare)
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Identification of Aminopyrimidine Regioisomers via Line Broadening Effects in 1H and 13C NMR Spectroscopy
- 2004
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Ingår i: Australian Journal of Chemistry. ; 57:11, s. 1079-1083
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Tidskriftsartikel (refereegranskat)abstract
- Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments.
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| 19. |
- Gasek, Nathan, et al.
(författare)
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Development of alginate and gelatin-based pleural and tracheal sealants
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061. ; 131, s. 222-235
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Tidskriftsartikel (refereegranskat)abstract
- Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. Statement of significance: Pneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.
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| 20. |
- Gei, Maga, et al.
(författare)
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Legume abundance along successional and rainfall gradients in Neotropical forests
- 2018
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:7
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Tidskriftsartikel (refereegranskat)abstract
- The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.
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| 21. |
- Levitis, E, et al.
(författare)
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Centering inclusivity in the design of online conferences-An OHBM-Open Science perspective
- 2021
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities.Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements of an online conference are still significant barriers to truly diverse participation: the tools used can be inaccessible for some individuals; the scheduling choices can favour some geographical locations; the set-up of the conference can provide more visibility to well-established researchers and reduce opportunities for early-career researchers. While acknowledging the benefits of an online setting, especially for individuals who have traditionally been underrepresented or excluded, we recognize that fostering social justice requires inclusivity to actively be centered in every aspect of online conference design.Here, we draw from the literature and from our own experiences to identify practices that purposefully encourage a diverse community to attend, participate in, and lead online conferences. Reflecting on how to design more inclusive online events is especially important as multiple scientific organizations have announced that they will continue offering an online version of their event when in-person conferences can resume.
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| 22. |
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| 23. |
- Riquelme, M. V. P., et al.
(författare)
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Demonstrating a Comprehensive Wastewater-Based Surveillance Approach That Differentiates Globally Sourced Resistomes
- 2022
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 56:21, s. 14982-14993
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Tidskriftsartikel (refereegranskat)abstract
- Wastewater-based surveillance (WBS) for disease monitoring is highly promising but requires consistent method-ologies that incorporate predetermined objectives, targets, and metrics. Herein, we describe a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage that enables assessment of 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends in ARGs, such as antibiotic concentrations. Across an internationally sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Regional trends in measured antibiotic concentrations differed from trends expected from public sales data. This could reflect unaccounted uses, captured only by the WBS approach. If properly benchmarked, antibiotic WBS might complement public sales and consumption statistics in the future. The WBS approach defined herein demonstrates multisite comparabyility and sensitivity to local/regional factors.
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| 24. |
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| 25. |
- Stevens, A., et al.
(författare)
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Gene expression signatures predict response to therapy with growth hormone
- 2021
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Ingår i: Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 21, s. 594-607
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant human growth hormone (r-hGH) is used as a therapeutic agent for disorders of growth including growth hormone deficiency (GHD) and Turner syndrome (TS). Treatment is costly and current methods to model response are inexact. GHD (n = 71) and TS patients (n = 43) were recruited to study response to r-hGH over 5 years. Analysis was performed using 1219 genetic markers and baseline (pre-treatment) blood transcriptome. Random forest was used to determine predictive value of transcriptomic data associated with growth response. No genetic marker passed the stringency criteria for prediction. However, we identified an identical set of genes in both GHD and TS whose expression could be used to classify therapeutic response to r-hGH with a high accuracy (AUC > 0.9). Combining transcriptomic markers with clinical phenotype was shown to significantly reduce predictive error. This work could be translated into a single genomic test linked to a prediction algorithm to improve clinical management. Trial registration numbers: NCT00256126 and NCT00699855.
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| 26. |
- Alme, Tomas Nordheim, et al.
(författare)
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Chronic fatigue syndromes: real illnesses that people can recover from
- 2023
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Ingår i: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 41:4, s. 372-376
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Tidskriftsartikel (refereegranskat)abstract
- The Oslo Chronic Fatigue Consortium consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brains response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.
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| 27. |
- Appelqvist, Hanna, et al.
(författare)
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Attenuation of the Lysosomal Death Pathway by Lysosomal Cholesterol Accumulation
- 2011
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Ingår i: American Journal of Pathology. - : American Society for Investigative Pathology (ASIP). - 0002-9440 .- 1525-2191. ; 178:2, s. 629-639
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Tidskriftsartikel (refereegranskat)abstract
- In the past decade, lysosomal membrane permeabilization (LMP) has emerged as a significant component of cell death signaling. The mechanisms by which lysosomal stability is regulated are not yet fully understood, but changes in the lysosomal membrane lipid composition have been suggested to be involved. Our aim was to investigate the importance of cholesterol in the regulation of lysosomal membrane permeability and its potential impact on apoptosis. Treatment of normal human fibroblasts with U18666A, an amphiphilic drug that inhibits cholesterol transport and causes accumulation of cholesterol in lysosomes, rescued cells from lysosome-dependent cell death induced by the lysosomotropic detergent 0-methyl-serine dodecylamide hydrochloride (MSDH), staurosporine (STS), or cisplatin. LMP was decreased by pretreating cells with U18666A, and there was a linear relationship between the cholesterol content of lysosomes and their resistance to permeabilization induced by MSDH. U18666A did not induce changes in expression or localization of 70-kDa heat shock proteins (Hsp70) or antiapoptotic Bcl-2 proteins known to protect the lysosomal membrane. Induction of autophagy also was excluded as a contributor to the protective mechanism. By using Chinese hamster ovary (CHO) cells with lysosomal cholesterol overload due to a mutation in the cholesterol transporting protein Niemann-Pick type C1 (NPC1), the relationship between lysosomal cholesterol accumulation and protection from lysosome-dependent cell death was confirmed. Cholesterol accumulation in lysosomes attenuates apoptosis by increasing lysosomal membrane stability.
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| 28. |
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| 29. |
- Ball, Sarah, et al.
(författare)
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Genetic and demographic vulnerability of adder populations : Results of a genetic study in mainland Britain
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors are often overlooked in conservation planning, despite their importance in small isolated populations. We used mitochondrial and microsatellite markers to investigate population genetics of the adder (Vipera berus) in southern Britain, where numbers are declining. We found no evidence for loss of heterozygosity in any of the populations studied. Genetic diversity was comparable across sites, in line with published levels for mainland Europe. However, further analysis revealed a striking level of relatedness. Genetic networks constructed from inferred first degree relationships suggested a high proportion of individuals to be related at a level equivalent to that of half-siblings, with rare inferred full-sib dyads. These patterns of relatedness can be attributed to the high philopatry and low vagility of adders, which creates high local relatedness, in combination with the polyandrous breeding system in the adder, which may offset the risk of inbreeding in closed populations. We suggest that reliance on standard genetic indicators of inbreeding and diversity may underestimate demographic and genetic factors that make adder populations vulnerable to extirpation. We stress the importance of an integrated genetic and demographic approach in the conservation of adders, and other taxa of similar ecology.
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| 30. |
- Barrett, J H, et al.
(författare)
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Investigation of interaction between N-acetyltransferase 2 and heterocyclic amines as potential risk factors for colorectal cancer
- 2003
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 24:2, s. 275-282
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Tidskriftsartikel (refereegranskat)abstract
- Fast N-acetyltransferase 2 (NAT2) acetylators may be at increased risk of colorectal cancer through the activation of carcinogenic heterocyclic amines (HA), which are produced by meat cooked at high temperatures and are found in cigarette smoke. A study of 500 incident colorectal cancer cases and population controls, matched for age, sex and general practitioner, was conducted in the UK to investigate this hypothesis. Usual meat intake and lifetime smoking habits were estimated using a detailed questionnaire administered by interview. Subjects also indicated how well cooked they ate their meat. Subjects were classified as fast or slow NAT2 acetylators on the basis of NAT2 genotype. Complete genotype data were available on 433 matched pairs. The risk of colorectal cancer showed a steady increase with meat intake, rising to an odds ratio of 1.51 [95% confidence interval (1.03, 2.23)] for the highest versus the lowest quartile, after adjustment for total energy intake, and this was even more pronounced for red meat [odds ratio 1.97 (1.30, 2.98)]. However, this effect was not influenced by the preference for well-done meat. Smoking was also associated with an increased risk [odds ratio 1.47 (1.10, 1.98) for ever- versus never-smokers]. In both cases and controls similar to40% of subjects were classified as fast acetylators, and the risks associated with (red) meat intake and smoking did not vary with NAT2 status. This study provides no support for the hypothesis that fast NAT2 acetylators are at increased risk of colorectal cancer, even if exposed to high levels of HA from well-cooked meat or smoking.
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| 31. |
- Capo, Eric, et al.
(författare)
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Lake sedimentary dna research on past terrestrial and aquatic biodiversity: Overview and recommendations
- 2021
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Ingår i: Quaternary. - : MDPI. - 2571-550X. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- The use of lake sedimentary DNA to track the long-term changes in both terrestrial and aquatic biota is a rapidly advancing field in paleoecological research. Although largely applied nowadays, knowledge gaps remain in this field and there is therefore still research to be conducted to ensure the reliability of the sedimentary DNA signal. Building on the most recent literature and seven original case studies, we synthesize the state-of-the-art analytical procedures for effective sampling, extraction, amplification, quantification and/or generation of DNA inventories from sedimentary ancient DNA (sedaDNA) via high-throughput sequencing technologies. We provide recommendations based on current knowledge and best practises.
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| 32. |
- 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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| 33. |
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| 34. |
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| 35. |
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| 36. |
- Greenhalf, William, et al.
(författare)
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Pancreatic Cancer hENT1 Expression and Survival From Gemcitabine in Patients From the ESPAC-3 Trial
- 2014
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:1, s. djt347-
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Tidskriftsartikel (refereegranskat)abstract
- Background Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection. Methods Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided. Results Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (chi(2)(1)=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (chi(2)(1)=9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (chi(2)(1) = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (chi(2)(1) = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald chi(2)(1) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald chi(2)(1) = 1.22; P = .27) patients. Conclusions Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.
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| 37. |
- Harder, Thomas, et al.
(författare)
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Towards a framework for evaluating and grading evidence in public health
- 2015
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Ingår i: Health Policy. - : Elsevier. - 0168-8510 .- 1872-6054. ; 119:6, s. 732-736
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Tidskriftsartikel (refereegranskat)abstract
- The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an international collaboration of public health institutes and universities which has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2012. Main objective is to define a framework for evaluating and grading evidence in the field of public health, with particular focus on infectious disease prevention and control. As part of the peer review process, an international expert meeting was held on 13-1 4 June 2013 in Berlin. Participants were members of the PRECEPT team and selected experts from national public health institutes, World Health Organization (WHO), and academic institutions. The aim of the meeting was to discuss the draft framework and its application to two examples from infectious disease prevention and control. This article introduces the draft PRECEPT framework and reports on the meeting, its structure, most relevant discussions and major conclusions.
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| 38. |
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| 39. |
- Hua, Jianyi, et al.
(författare)
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Oxi4503, a novel vascular targeting agent: effects on blood flow and antitumor activity in comparison to combretastatin A-4 phosphate.
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:2B, s. 1433-1440
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Tidskriftsartikel (refereegranskat)abstract
- Oxi4503, which is the diphosphate prodrug of combretastatin A1, is a novel vascular targeting agent from the combretastatin family. Another member of this family, Combretastatin A-4 phosphate (CA4P), is a well-characterized vascular targeting agent already being evaluated in clinical trials. The potential for tumor vascular targeting by Oxi4503 was assessed in a mouse system. This approach aims to shut down the established tumor vasculature, leading to the development of extensive tumor cell necrosis. The vascular effects of Oxi4503 were assessed in the s.c. implanted MDA-MB-231 adenocarcinoma and the MHEC5-T hemangio-endothelioma in SCID mice and in a range of normal tissues. Blood flow was measured by i.v. injection of fluorescence beads, while quantitative fluorescence microscopy was used to measure the spatial heterogeneity of blood flow in tumor sections. Oxi4503 induced the shutdown of tumor blood vessels in a dose-dependent pattern with an ED50 at 3 mg/kg in contrast to 43 mg/kg of CA4P. Quantitative fluorescence microscopy showed that Oxi4503 increased the spatial heterogeneity in tumor blood flow. Oxi4503 affected peripheral tumor regions less than central regions, although this was not as pronounced as seen with CA4P, where only central regions were affected. The vascular shutdown induced by administration of Oxi4503 at a dose of 6 mg/kg resulted in extensive cell loss 24 hours following treatment, which translated into a significant effect on tumor growth. Tumor growth was completely repressed at doses above 12.5 mg/kg of Oxi4503, while doses above 25 mg/kg showed tumor regression and even complete regression in some animals. These results are promising for the use of Oxi4503 as a tumor vascular targeting agent. Moreover the potent antitumor effect when administered as a single agent suggests a different activity profile than CA4P.
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| 40. |
- Kemp, Samuel V., et al.
(författare)
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A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM)
- 2017
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 196:12, s. 1535-1543
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach. Objectives: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation.Methods: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months.Measurements and Main Results: Ninety seven subjects were randomized toEBV(n = 65) or SoC(n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P < 0.001). Improvements were maintained at 6 months: EBV 56.3% versus SoC 3.2% (P < 0.001), with a mean +/- SD change in FEV1 at 6 months of 20.7 +/- 29.6% and -8.6 +/- 13.0%, respectively. A total of 89.8% of EBV subjects had target lobe volume reduction greater than or equal to 350 ml, mean 1.09 +/- 0.62 L (P < 0.001). Between-group differences for changes at 6 months were statistically and clinically significant: Delta EBV-SoC for residual volume, -700 ml; 6-minute-walk distance, +78.7 m; St. George's Respiratory Questionnaire score, -6.5 points; modified Medical Research Council dyspnea score, -0.6 points; and BODE(body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 21.8 points (all P < 0.05). Pneumothorax was the most common adverse event, occurring in 19 of 65 (29.2%) of EBV subjects.Conclusions: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile.
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| 41. |
- Kim, Woojin Scott, et al.
(författare)
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Increased ATP-binding cassette transporter A1 expression in Alzheimer's disease hippocampal neurons
- 2010
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 21:1, s. 193-205
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Tidskriftsartikel (refereegranskat)abstract
- ATP-binding cassette transporter A1 (ABCA1) reduces amyloid-beta burden in transgenic mouse models of Alzheimer's disease (AD). Associations between ABCA1 polymorphisms and AD risk are also established. Little is known regarding the regulation of ABCA1 expression in the brain and how this may be affected by AD. In the present study we assessed ABCA1 mRNA and protein expression in the hippocampus of AD cases compared to controls. ABCA1 was clearly expressed in hippocampal neurons and expression was increased two- to three-fold in AD cases. The increased hippocampal ABCA1 expression was associated with increased APOE and PUMA gene expression, implying an association with neuronal stress. Consistent with this, treatment of SK-N-SH neurons with amyloid-beta peptide resulted in a 48% loss in survival and a significant upregulation of ABCA1, APOE, and PUMA gene expression. Studies in young (2 month) and old (12 month) transgenic mice expressing a familial AD form of human amyloid-beta protein precursor and presenilin-1 revealed a significant age-dependent upregulation of hippocampal Abca1 compared to wild-type control mice. However, hippocampal Apoe and Puma gene expression were not correlated with increased Abca1 expression in mice. Our data indicate that ABCA1 is upregulated in AD hippocampal neurons potentially via an amyloid-beta-mediated pathway.
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| 42. |
- Lloyd, MD, et al.
(författare)
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Studies on the active site of deacetoxycephalosporin C synthase
- 1999
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Ingår i: JOURNAL OF MOLECULAR BIOLOGY. - : ACADEMIC PRESS LTD. - 0022-2836. ; 287:5, s. 943-960
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Tidskriftsartikel (refereegranskat)abstract
- The Fe(II) and 2-oxogolutarate-dependent dioxygenase deacetoxycephalosporin C synthase (DAOCS) from Streptomyces clavuligerus was expressed at ca 25% of total soluble protein in Escherichia coli and purified by an efficient large-scale procedure. Purified
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| 43. |
- Meurling, Sara, et al.
(författare)
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Occurrence of Batrachochytrium dendrobatidis in Sweden : higher infection prevalence in southern species
- 2020
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Ingår i: Diseases of Aquatic Organisms. - : Inter-Research Science Center. - 0177-5103 .- 1616-1580. ; 140, s. 209-218
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Tidskriftsartikel (refereegranskat)abstract
- The chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused worldwide declines in amphibian populations. While Bd is widespread in southern and central Europe, its occurrence and distribution in northernmost Europe is mostly unknown. We surveyed for Bd in breeding anurans in Sweden by sampling 1917 amphibians from 101 localities and 3 regions in Sweden (southern, northern and central). We found that Bd was widespread in southern and central Sweden, occurring in all 9 investigated species and in 45.5% of the 101 localities with an overall prevalence of 13.8%. No infected individuals were found in the 4 northern sites sampled. The records from central Sweden represent the northernmost records of Bd in Europe. While the proportion of sites positive for Bd was similar between the southern and central regions, prevalence was much higher in the southern region. This was because southern species with a distribution mainly restricted to southernmost Sweden had a higher prevalence than widespread generalist species. The nationally red-listed green toad Bufotes variabilis and the fire-bellied toad Bombina bombina had the highest prevalence (61.4 and 48.9%, respectively). Across species, Bd prevalence was strongly positively, correlated with water temperature at the start of egg laying. However, no individuals showing visual signs of chytridiomycosis were found in the field. These results indicate that Bd is widespread and common in southern and central Sweden with southern species, breeding in higher temperatures and with longer breeding periods, having higher prevalence. However, the impact of Bd on amphibian populations in northernmost Europe remains unknown.
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| 44. |
- Nordin-Bates, Sanna M, et al.
(författare)
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Injury, imagery, and self-esteem in dance : Healthy minds in injured bodies?
- 2011
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Ingår i: Journal of Dance Medicine and Science. - 1089-313X. ; 15:2, s. 76-85
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate a selection of psychological variables (help-seeking behaviors, mental imagery, self-esteem) in relation to injury among UK dancers. We recruited 216 participants from eight dance styles and six levels of involvement. It was found that 83.5% of the participants had experienced at least one injury in the past year. The most common response to injury was to inform someone, and most continued to dance when injured, albeit carefully. Physical therapy was the most common treatment sought when an injury occurred (38.1%), and dancers seemed to follow recommendations offered. Injured and non-injured dancers did not differ in their imagery frequencies (facilitative, debilitative, or injury-related) and scored similarly (and relatively high) in self-esteem. Neither facilitative nor debilitative imagery was correlated with self-esteem, but dancers who engaged in more facilitative imagery in general also reported doing so when injured. Altogether, it appears that injury is not related to dancers' self-esteem or imagery, at least not when injuries are mild or moderate. Even so, such conclusions should be made with caution, given that most dancers do sustain at least one injury each year.
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| 45. |
- Roelofs, T. J. M., et al.
(författare)
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Optimization of whole-brain rabies virus tracing technology for small cell populations
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0-3.0x10(7) genomic copies per mu l of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.
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| 46. |
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| 47. |
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| 48. |
- Tobias, J., et al.
(författare)
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A New Strategy Toward B Cell-Based Cancer Vaccines by Active Immunization With Mimotopes of Immune Checkpoint Inhibitors
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic monoclonal antibodies (mAbs), targeting tumor antigens, or immune checkpoints, have demonstrated a remarkable anti-tumor effect against various malignancies. However, high costs for mono- or combination therapies, associated with adverse effects or possible development of resistance in some patients, warrant further development and modification to gain more flexibility for this immunotherapy approach. An attractive alternative to passive immunization with therapeutic antibodies might be active immunization with mimotopes (B-cell peptides) representing the mAbs' binding epitopes, to activate the patient's own anti-tumor immune response following immunization. Here, we identified and examined the feasibility of inducing anti-tumor effectsin vivofollowing active immunization with a mimotope of the immune checkpoint programmed cell death 1 (PD1), alone or in combination with a Her-2/neu B-cell peptide vaccine. Overlapping peptides spanning the extracellular domains of human PD1 (hPD1) were used to identify hPD1-derived mimotopes, using the therapeutic mAb Nivolumab as a proof of concept. Additionally, forin vivoevaluation in a tumor mouse model, a mouse PD1 (mPD1)-derived mimotope was identified using an anti-mPD1 mAb with mPD1/mPDL-1 blocking capacity. The identified mimotopes were characterized byin vitroassays, including a reporter cell-based assay, and their anti-tumor effects were evaluated in a syngeneic tumor mouse model stably expressing human Her-2/neu. The identified PD1-derived mimotopes were shown to significantly block the mAbs' capacity in inhibiting the respective PD1/PD-L1 interactions. A significant reduction in tumor growthin vivowas observed following active immunization with the mPD1-derived mimotope, associated with a significant reduction in proliferation and increased apoptotic rates in the tumors. Particularly, combined vaccination with the mPD1-derived mimotope and a multiple B-cell epitope Her-2/neu vaccine potentiated the vaccine's anti-tumor effect. Our results suggest active immunization with mimotopes of immune checkpoint inhibitors either as monotherapy or as combination therapy with tumor-specific vaccines, as a new strategy for cancer treatment.
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