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2. |
- 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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3. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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4. |
- Alves, Gustavo R., et al.
(författare)
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International Cooperation for Remote Laboratory Use
- 2018
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Ingår i: Contributions to Higher Engineering Education. - Singapore : Springer. - 9789811089176 ; , s. 1-31
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Bokkapitel (refereegranskat)abstract
- Experimenting is fundamental to the training process of all scientists and engineers. While experiments have been traditionally done inside laboratories, the emergence of Information and Communication Technologies added two alternatives accessible anytime, anywhere. These two alternatives are known as virtual and remote laboratories and are sometimes indistinguishably referred as online laboratories. Similarly to other instructional technologies, virtual and remote laboratories require some effort from teachers in integrating them into curricula, taking into consideration several factors that affect their adoption (i.e., cost) and their educational effectiveness (i.e., benefit). This chapter analyzes these two dimensions and sustains the case where only through international cooperation it is possible to serve the large number of teachers and students involved in engineering education. It presents an example in the area of electrical and electronics engineering, based on a remote laboratory named Virtual Instruments System in Reality, and it then describes how a number of European and Latin American institutions have been cooperating under the scope of an Erasmus+ project, for spreading its use in Brazil and Argentina.
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5. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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6. |
- Cardwell, Chris R, et al.
(författare)
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Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:11, s. 2215-2225
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
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7. |
- MacDougall, Andrew S., et al.
(författare)
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Widening global variability in grassland biomass since the 1980s
- 2024
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X.
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Tidskriftsartikel (refereegranskat)abstract
- Global change is associated with variable shifts in the annual production of aboveground plant biomass, suggesting localized sensitivities with unclear causal origins. Combining remotely sensed normalized difference vegetation index data since the 1980s with contemporary field data from 84 grasslands on 6 continents, we show a widening divergence in site-level biomass ranging from +51% to −34% globally. Biomass generally increased in warmer, wetter and species-rich sites with longer growing seasons and declined in species-poor arid areas. Phenological changes were widespread, revealing substantive transitions in grassland seasonal cycling. Grazing, nitrogen deposition and plant invasion were prevalent in some regions but did not predict overall trends. Grasslands are undergoing sizable changes in production, with implications for food security, biodiversity and carbon storage especially in arid regions where declines are accelerating.
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8. |
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9. |
- Eriksson, Gunilla M., et al.
(författare)
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Occupations of Older Adults : A Cross Cultural Description
- 2011
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Ingår i: OTJR (Thorofare, N.J.). - : SAGE Publications. - 1539-4492 .- 1938-2383. ; 31:4, s. 182-192
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Tidskriftsartikel (refereegranskat)abstract
- Participation in everyday occupations influences people's health and well-being. To enable individuals to do the activities they want and need to do is the main concern of occupational therapy practice. Many daily occupations are universal, but they also depend on culture. The development of the Activity Card Sort in eight countries has offered the opportunity to describe occupations across cultures. In the developmental process of culturally relevant versions of the Activity Card Sort by occupational therapists in each country, the instrument versions included samples of older adults (N = 468). These data are used in the current description with the aim of identifying central activities across cultures and central activities for Asian and Western cultures. Ten activities were identified as being central across cultures (i.e., more than half of the older adults in all eight countries performed them). They were the following: shopping in a store, doing grocery shopping, doing dishes, doing laundry, reading books or magazines, sitting and thinking, watching television, listening to radio or music, visiting with friends and relatives, and talking on the telephone. Further, 16 additional activities central to Asian culture and 18 activities central to Western culture were identified. The identification of central activities deepens knowledge of activities with cultural significance. This knowledge is needed in clinical practice and multicultural research. This description provides a starting point for further exploration of everyday occupations among older adults.
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10. |
- Fitzsimmons-Craft, Ellen E., et al.
(författare)
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Harnessing mobile technology to reduce mental health disorders in college populations : A randomized controlled trial study protocol
- 2021
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- About a third of college students struggle with anxiety, depression, or an eating disorder, and only 20?40% of college students with mental disorders receive treatment. Inadequacies in mental health care delivery result in prolonged illness, disease progression, poorer prognosis, and greater likelihood of relapse, highlighting the need for a new approach to detect mental health problems and engage college students in services. We have developed a transdiagnostic, low-cost mobile mental health targeted prevention and intervention platform that uses population-level screening to engage college students in tailored services that address common mental health problems. We will test the impact of this mobile mental health platform for service delivery in a large-scale trial across 20+ colleges. Students who screen positive or at high-risk for clinical anxiety, depression, or an eating disorder and who are not currently engaged in mental health services (N = 7884) will be randomly assigned to: 1) intervention via the mobile mental health platform; or 2) referral to usual care (i.e., campus health or counseling center). We will test whether the mobile mental health platform, compared to referral, is associated with improved uptake, reduced clinical cases, disorder-specific symptoms, and improved quality of life and functioning. We will also test mediators, predictors, and moderators of improved mental health outcomes, as well as stakeholder-relevant outcomes, including cost-effectiveness and academic performance. This population-level approach to service engagement has the potential to improve mental health outcomes for the millions of students enrolled in U.S. colleges and universities.
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11. |
- Izadi, Zara, et al.
(författare)
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Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease : an observational study
- 2022
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Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 4:9, s. e603-e613
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally.Methods: In this observational study, we derived individual-level data on adults (aged 18–99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death.Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01–1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10–1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02–1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00–1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88–1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44–0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74–0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69–0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1–9·5]; p=0·14).Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities.
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13. |
- Akanyeti, Otar, et al.
(författare)
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Fish-inspired segment models for undulatory steady swimming
- 2022
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Ingår i: Bioinspiration & Biomimetics. - : IOP Publishing. - 1748-3182 .- 1748-3190. ; 17:4
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Tidskriftsartikel (refereegranskat)abstract
- Many aquatic animals swim by undulatory body movements and understanding the diversity of these movements could unlock the potential for designing better underwater robots. Here, we analyzed the steady swimming kinematics of a diverse group of fish species to investigate whether their undulatory movements can be represented using a series of interconnected multi-segment models, and if so, to identify the key factors driving the segment configuration of the models. Our results show that the steady swimming kinematics of fishes can be described successfully using parsimonious models, 83% of which had fewer than five segments. In these models, the anterior segments were significantly longer than the posterior segments, and there was a direct link between segment configuration and swimming kinematics, body shape, and Reynolds number. The models representing eel-like fishes with elongated bodies and fishes swimming at high Reynolds numbers had more segments and less segment length variability along the body than the models representing other fishes. These fishes recruited their anterior bodies to a greater extent, initiating the undulatory wave more anteriorly. Two shape parameters, related to axial and overall body thickness, predicted segment configuration with moderate to high success rate. We found that head morphology was a good predictor of its segment length. While there was a large variation in head segments, the length of tail segments was similar across all models. Given that fishes exhibited variable caudal fin shapes, the consistency of tail segments could be a result of an evolutionary constraint tuned for high propulsive efficiency. The bio-inspired multi-segment models presented in this study highlight the key bending points along the body and can be used to decide on the placement of actuators in fish-inspired robots, to model hydrodynamic forces in theoretical and computational studies, or for predicting muscle activation patterns during swimming.
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15. |
- Callini, Elsa, et al.
(författare)
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Complex and liquid hydrides for energy storage
- 2016
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Ingår i: Applied Physics A. - : Springer Science and Business Media LLC. - 0947-8396 .- 1432-0630. ; 122:4
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Tidskriftsartikel (refereegranskat)abstract
- The research on complex hydrides for hydrogen storage was initiated by the discovery of Ti as a hydrogen sorption catalyst in NaAlH4 by Boris Bogdanovic in 1996. A large number of new complex hydride materials in various forms and combinations have been synthesized and characterized, and the knowledge regarding the properties of complex hydrides and the synthesis methods has grown enormously since then. A significant portion of the research groups active in the field of complex hydrides is collaborators in the International Energy Agreement Task 32. This paper reports about the important issues in the field of complex hydride research, i.e. the synthesis of borohydrides, the thermodynamics of complex hydrides, the effects of size and confinement, the hydrogen sorption mechanism and the complex hydride composites as well as the properties of liquid complex hydrides. This paper is the result of the collaboration of several groups and is an excellent summary of the recent achievements.
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16. |
- Dahlberg, C. Johan, 1978-, et al.
(författare)
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Population differentiation in timing of development in a forest herb associated with local climate and canopy closure
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Our knowledge of how plant seasonal development is related to local versus larger-scale environmental variation is limited. We investigated differentiation in the timing of vegetative and reproductive development among populations of the forest herb Lathyrus vernus over different spatial scales. We predicted earlier development and shorter development time for populations from a colder, northern region compared to populations from a warmer, southern region. Also, we predicted earlier and shorter development within regions to be associated with colder temperatures and higher proportions of deciduous trees at their sites of origin. Lastly, we predicted that earlier flowering is strongly correlated with earlier start of development. To examine these predictions, we conducted a common garden study, and compared the development of 10 northern and 10 southern Swedish L. vernus populations. Start of development, development time and start of flowering did not differ between populations from the two regions in contrast to our prediction. Within the southern region, start of flowering was earlier in populations from colder sites, while start of development was earlier with colder temperatures within the northern region. Start of flowering occurred earlier in southern populations from sites with higher proportion of deciduous trees. Thus, the prediction for the timing of development within regions was partly confirmed. However, vegetative and reproductive development was not simultaneously influenced by temperature and proportion of deciduous trees within regions, possibly due to the negative correlation between vegetative growth and development time. This implies that earlier start of development or shorter development time not necessarily correspond to earlier start of flowering or vice versa. Overall, the results suggest that smaller scale effects within region, such as temperature and interspecific competition for light, was more important for the timing of development than the larger scale gradients between regions. Lastly, the population differentiation across gradients of temperature and proportion of deciduous trees implies that populations may adapt to long-term changes in light or climatic conditions, and differ in their short-term response to climate change.
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17. |
- Delvallée, Clarisse, et al.
(författare)
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A BBS1 SVA F retrotransposon insertion is a frequent cause of Bardet-Biedl syndrome
- 2021
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Ingår i: Clinical Genetics. - : John Wiley & Sons. - 0009-9163 .- 1399-0004. ; 99:2, s. 318-324
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Tidskriftsartikel (refereegranskat)abstract
- Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinitis pigmentosa, obesity, polydactyly, cognitive impairment and renal failure. Pathogenic variants in 24 genes account for the molecular basis of >80% of cases. Toward saturated discovery of the mutational basis of the disorder, we carefully explored our cohorts and identified a hominid-specific SINE-R/VNTR/Alu type F (SVA-F) insertion in exon 13 of BBS1 in eight families. In six families, the repeat insertion was found in trans with c.1169 T > G, p.Met390Arg and in two families the insertion was found in addition to other recessive BBS loci. Whole genome sequencing, de novo assembly and SNP array analysis were performed to characterize the genomic event. This insertion is extremely rare in the general population (found in 8 alleles of 8 BBS cases but not in >10 800 control individuals from gnomAD-SV) and due to a founder effect. Its 2435 bp sequence contains hallmarks of LINE1 mediated retrotransposition. Functional studies with patient-derived cell lines confirmed that the BBS1 SVA-F is deleterious as evidenced by a significant depletion of both mRNA and protein levels. Such findings highlight the importance of dedicated bioinformatics pipelines to identify all types of variation.
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18. |
- Dent, Elsa, et al.
(författare)
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Recent developments in frailty identification, management, risk factors and prevention : A narrative review of leading journals in geriatrics and gerontology
- 2023
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Ingår i: Ageing Research Reviews. - 1568-1637 .- 1872-9649. ; 91
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Forskningsöversikt (refereegranskat)abstract
- Frailty is an age-related clinical condition characterised by an increased susceptibility to stressors and an elevated risk of adverse outcomes such as mortality. In the light of global population ageing, the prevalence of frailty is expected to soar in coming decades. This narrative review provides critical insights into recent developments and emerging practices in frailty research regarding identification, management, risk factors, and prevention. We searched journals in the top two quartiles of geriatrics and gerontology (from Clarivate Journal Citation Reports) for articles published between 01 January 2018 and 20 December 2022. Several recent developments were identified, including new biomarkers and biomarker panels for frailty screening and diagnosis, using artificial intelligence to identify frailty, and investigating the altered response to medications by older adults with frailty. Other areas with novel developments included exercise (including technology-based exercise), multidimensional interventions, person-centred and integrated care, assistive technologies, analysis of frailty transitions, risk-factors, clinical guidelines, COVID-19, and potential future treatments. This review identified a strong need for the implementation and evaluation of cost-effective, community-based interventions to manage and prevent frailty. Our findings highlight the need to better identify and support older adults with frailty and involve those with frailty in shared decision-making regarding their care.
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19. |
- Di Santo, Valentina, et al.
(författare)
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Convergence of undulatory swimming kinematics across a diversity of fishes
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:49
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Tidskriftsartikel (refereegranskat)abstract
- Fishes exhibit an astounding diversity of locomotor behaviors from classic swimming with their body and fins to jumping, flying, walking, and burrowing. Fishes that use their body and caudal fin (BCF) during undulatory swimming have been traditionally divided into modes based on the length of the propulsive body wave and the ratio of head:tail oscillation amplitude: anguilliform, subcarangiform, carangiform, and thunniform. This classification was first proposed based on key morphological traits, such as body stiffness and elongation, to group fishes based on their expected swimming mechanics. Here, we present a comparative study of 44 diverse species quantifying the kinematics and morphology of BCF-swimming fishes. Our results reveal that most species we studied share similar oscillation amplitude during steady locomotion that can be modeled using a second-degree order polynomial. The length of the propulsive body wave was shorter for species classified as anguilliform and longer for those classified as thunniform, although substantial variability existed both within and among species. Moreover, there was no decrease in head:tail amplitude from the anguilliform to thunniform mode of locomotion as we expected from the traditional classification. While the expected swimming modes correlated with morphological traits, they did not accurately represent the kinematics of BCF locomotion. These results indicate that even fish species differing as substantially in morphology as tuna and eel exhibit statistically similar two-dimensional midline kinematics and point toward unifying locomotor hydrodynamic mechanisms that can serve as the basis for understanding aquatic locomotion and controlling biomimetic aquatic robots.
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20. |
- Fernandes, Elsa C Antunes, et al.
(författare)
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Activation and potentiation of human GABAA receptors by non-dioxin-like PCBs depends on chlorination pattern
- 2010
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 118:1, s. 183-90
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Tidskriftsartikel (refereegranskat)abstract
- The neurotoxic potential of non-dioxin-like polychlorinated biphenyls (NDL-PCBs) is characterized by disruption of presynaptic processes, including calcium homeostasis and neurotransmitter transport. Recently, using a limited set of congeners, we demonstrated that PCB28 and PCB52 can potentiate postsynaptic GABA(A) receptors. In the present study, effects of 20 NDL-PCBs and 2 dioxin-like PCBs, selected based on their chemical variation and abundance in the environment, on human GABA(A) receptors were investigated. GABA(A) receptors were expressed in Xenopus oocytes, and NDL-PCB effects were determined using the two-electrode voltage-clamp technique. Results demonstrate that lower chlorinated PCB19, PCB28, PCB47, PCB51, PCB52, PCB95, and PCB100 act as a partial agonists (at low receptor occupancy), i.e., potentiating the receptor response during coapplication with GABA (at EC(20)). Importantly, PCB19, PCB47, PCB51, and PCB100 can also act as full agonist, i.e., activate the GABA(A) receptor in the absence of GABA. Potentiation and activation of the GABA(A) receptor is concentration dependent and limited to NDL-PCBs that have 3-5 chlorine atoms, 1-3 ortho-substitutions, an equal number (0-1) of meta-substitutions on both phenyl rings, and do not have an adjacent para- and meta-substitution on the same phenyl ring. Activation and potentiation of the GABA(A) receptor by PCB47, the most potent congener (lowest observed effect concentration of 10nM), is attenuated when coapplied with PCB19, PCB28, PCB153, or PCB180, indicative for competitive binding. Considering the importance of GABA-ergic signaling for brain development, motor coordination, learning, and memory, this mode of action can contribute to the previously observed NDL-PCB-induced neurobehavioral and neurodevelopmental effects and should be included in human risk assessment.
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21. |
- Hansén Nord, Karolin, et al.
(författare)
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Recurrent chromosome 22 deletions in osteoblastoma affect inhibitors of the wnt/beta-catenin signaling pathway.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Osteoblastoma is a bone forming tumor with histological features highly similar to osteoid osteoma; the discrimination between the tumor types is based on size and growth pattern. The vast majority of osteoblastomas are benign but there is a group of so-called aggressive osteoblastomas that can be diagnostically challenging at the histopathological level. The genetic aberrations required for osteoblastoma development are not known and no genetic difference between conventional and aggressive osteoblastoma has been reported. In order to identify recurrent genomic aberrations of importance for tumor development we applied cytogenetic and/or SNP array analyses on nine conventional and two aggressive osteoblastomas. The conventional osteoblastomas showed few or no acquired genetic aberrations while the aggressive tumors displayed heavily rearranged genomes. In one of the aggressive osteoblastomas, three neighboring regions in chromosome band 22q12 were homozygously deleted. Hemizygous deletions of these regions were found in two additional cases, one aggressive and one conventional. In total, 10 genes were recurrently and homozygously lost in osteoblastoma. Four of them are functionally involved in regulating osteogenesis and/or tumorigenesis. MN1 and NF2 have previously been implicated in the development of leukemia and solid tumors, and ZNRF3 and KREMEN1 are inhibitors of the Wnt/beta-catenin signaling pathway. In line with deletions of the latter two genes, high beta-catenin protein expression has previously been reported in osteoblastoma and aberrations affecting the Wnt/beta-catenin pathway have been found in other bone lesions, including osteoma and osteosarcoma.
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22. |
- Hendriks, Hester S., et al.
(författare)
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PCB-47, PBDE-47, and 6-OH-PBDE-47 Differentially Modulate Human GABA(A) and alpha(4)beta(2) Nicotinic Acetylcholine Receptors
- 2010
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Ingår i: Toxicological Sciences. - : Oxford University Press (OUP). - 1096-6080 .- 1096-0929. ; 118:2, s. 635-642
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Tidskriftsartikel (refereegranskat)abstract
- Polychlorinated biphenyls (PCBs) and the structurally related polybrominated diphenyl ethers (PBDEs) are abundant persistent organic pollutants that exert several comparable neurotoxic effects. Importantly, hydroxylated metabolites of PCBs and PBDEs have an increased neurotoxic potency. Recently, we demonstrated that PCBs can act as (partial) agonist on GABA(A) neurotransmitter receptors, with PCB-47 being the most potent congener. It is, however, unknown whether PBDE-47 and its metabolite 6-OH-PBDE-47 exert similar effects and if these effects are limited to GABA(A) receptors only. We therefore investigated effects of PCB-47, PBDE-47, and 6-OH-PBDE-47 on the inhibitory GABA(A) and excitatory alpha(4)beta(2) nicotinic acetylcholine (nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Since human exposure is generally not limited to individual compounds, experiments with binary mixtures were also performed. The results demonstrate that PCB-47 and 6-OH-PBDE-47 act as full and partial agonist on the GABA(A) receptor. However, both congeners act as antagonist on the nACh receptor. PBDE-47 does not affect either type of receptor. Binary mixtures of PCB-47 and 6-OH-PBDE-47 induced an additive activation as well as potentiation of GABA(A) receptors, whereas this mixture resulted in an additive inhibition of nACh receptors. Binary mixtures of PBDE-47 and 6-OH-PBDE-47 yielded similar effects as 6-OH-PBDE-47 alone. These findings demonstrate that GABA(A) and nACh receptors are affected differently by PCB-47 and 6-OH-PBDE-47, with inhibitory GABA(A)-mediated signaling being potentiated and excitatory alpha(4)beta(2) nACh-mediated signaling being inhibited. Considering these opposite actions and the additive interaction of the congeners, these effects are likely to be augmented in vivo.
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23. |
- Jatuworapruk, Kanon, et al.
(författare)
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Characteristics and Outcomes of People With Gout Hospitalized Due to COVID-19 : Data From the COVID-19 Global Rheumatology Alliance Physician-Reported Registry
- 2022
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Ingår i: ACR Open Rheumatology. - : John Wiley & Sons. - 2578-5745. ; 4:11, s. 948-953
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo describe people with gout who were diagnosed with coronavirus disease 2019 (COVID-19) and hospitalized and to characterize their outcomes.MethodsData on patients with gout hospitalized for COVID-19 between March 12, 2020, and October 25, 2021, were extracted from the COVID-19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID-19 outcomes including oxygenation or ventilation support and death.ResultsOne hundred sixty-three patients with gout who developed COVID-19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre-COVID-19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID-19-related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities.ConclusionThis cohort of people with gout and COVID-19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID-19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.
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24. |
- Johansson, Henrik J., et al.
(författare)
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Breast cancer quantitative proteome and proteogenomic landscape
- 2019
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
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25. |
- Kahrs, Birgitte H., et al.
(författare)
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Fetal rotation during vacuum extractions for prolonged labor : a prospective cohort study
- 2018
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349. ; 97:8, s. 998-1005
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The aim of the study was to investigate fetal head rotation during vacuum extraction. Material and methods: We conducted a prospective cohort study from November 2013 to July 2016 in seven European hospitals. Fetal head position was determined with transabdominal or transperineal ultrasound and categorized as occiput anterior (OA), occiput transverse (OT) or occiput posterior (OP) position. Main outcome was the proportion of fetuses rotating during vacuum extraction. Secondary outcomes were conversion of delivery method, duration of vacuum extraction, umbilical artery pH <7.10 and agreement between clinical and ultrasound assessments. Results: The study population comprised 165 women. During vacuum extraction 117/119 (98%) remained in OA and two fetuses rotated to OP position. Rotation from OT to OA position occurred in 14/19 (74%) and to OP position in 5/19 (26%). Rotation from OP to OA position occurred in 15/25 (60%), and 10/25 (40%) fetuses remained in OP position. Delivery information was missing in two cases. The conversion rate from vacuum extraction to cesarean section or forceps was 10% in the OA group vs. 23% in the non-OA group; p < 0.05. The estimated duration of vacuum extraction was significantly shorter in OA fetuses, 7 min vs. 10 min (log rank test p < 0.01). There was no significant difference in umbilical artery pH < 7.10 between OA and non-OA position. Cohens Kappa of agreement between clinical and ultrasound assessments was 0.42 (95% CI 0.26–0.57). Conclusion: Most fetuses in OP or OT positions rotated to OA position during vacuum extraction, but the proportion of failed vacuum extractions remained high.
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