| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Lind, Lars, et al.
(författare)
-
Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
-
Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
|
|
| 8. |
- Bixby, H., et al.
(författare)
-
Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
-
Tidskriftsartikel (refereegranskat)abstract
- Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Taddei, C, et al.
(författare)
-
Repositioning of the global epicentre of non-optimal cholesterol
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
-
Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Pelletier, F., et al.
(författare)
-
Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
-
Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
|
|
| 18. |
- Kattge, Jens, et al.
(författare)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Tidskriftsartikel (refereegranskat)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 19. |
|
|
| 20. |
- Fabian, ID, et al.
(författare)
-
Travel burden and clinical presentation of retinoblastoma: analysis of 1024 patients from 43 African countries and 518 patients from 40 European countries
- 2021
-
Ingår i: The British journal of ophthalmology. - : BMJ. - 1468-2079 .- 0007-1161. ; 105:10, s. 1435-1443
-
Tidskriftsartikel (refereegranskat)abstract
- The travel distance from home to a treatment centre, which may impact the stage at diagnosis, has not been investigated for retinoblastoma, the most common childhood eye cancer. We aimed to investigate the travel burden and its impact on clinical presentation in a large sample of patients with retinoblastoma from Africa and Europe.MethodsA cross-sectional analysis including 518 treatment-naïve patients with retinoblastoma residing in 40 European countries and 1024 treatment-naïve patients with retinoblastoma residing in 43 African countries.ResultsCapture rate was 42.2% of expected patients from Africa and 108.8% from Europe. African patients were older (95% CI −12.4 to −5.4, p<0.001), had fewer cases of familial retinoblastoma (95% CI 2.0 to 5.3, p<0.001) and presented with more advanced disease (95% CI 6.0 to 9.8, p<0.001); 43.4% and 15.4% of Africans had extraocular retinoblastoma and distant metastasis at the time of diagnosis, respectively, compared to 2.9% and 1.0% of the Europeans. To reach a retinoblastoma centre, European patients travelled 421.8 km compared to Africans who travelled 185.7 km (p<0.001). On regression analysis, lower-national income level, African residence and older age (p<0.001), but not travel distance (p=0.19), were risk factors for advanced disease.ConclusionsFewer than half the expected number of patients with retinoblastoma presented to African referral centres in 2017, suggesting poor awareness or other barriers to access. Despite the relatively shorter distance travelled by African patients, they presented with later-stage disease. Health education about retinoblastoma is needed for carers and health workers in Africa in order to increase capture rate and promote early referral.
|
|
| 21. |
- Tinetti, G., et al.
(författare)
-
A chemical survey of exoplanets with ARIEL
- 2018
-
Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 46:1, s. 135-209
-
Tidskriftsartikel (refereegranskat)abstract
- Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Beale, M. A., et al.
(författare)
-
Global phylogeny of Treponema pallidum lineages reveals recent expansion and spread of contemporary syphilis
- 2021
-
Ingår i: Nature Microbiology. - : Springer Science and Business Media LLC. - 2058-5276. ; 6:12
-
Tidskriftsartikel (refereegranskat)abstract
- Syphilis, which is caused by the sexually transmitted bacterium Treponema pallidum subsp. pallidum, has an estimated 6.3 million cases worldwide per annum. In the past ten years, the incidence of syphilis has increased by more than 150% in some high-income countries, but the evolution and epidemiology of the epidemic are poorly understood. To characterize the global population structure of T. pallidum, we assembled a geographically and temporally diverse collection of 726 genomes from 626 clinical and 100 laboratory samples collected in 23 countries. We applied phylogenetic analyses and clustering, and found that the global syphilis population comprises just two deeply branching lineages, Nichols and SS14. Both lineages are currently circulating in 12 of the 23 countries sampled. We subdivided T. p.pallidum into 17 distinct sublineages to provide further phylodynamic resolution. Importantly, two Nichols sublineages have expanded clonally across 9 countries contemporaneously with SS14. Moreover, pairwise genome analyses revealed examples of isolates collected within the last 20 years from 14 different countries that had genetically identical core genomes, which might indicate frequent exchange through international transmission. It is striking that most samples collected before 1983 are phylogenetically distinct from more recently isolated sublineages. Using Bayesian temporal analysis, we detected a population bottleneck occurring during the late 1990s, followed by rapid population expansion in the 2000s that was driven by the dominant T. pallidum sublineages circulating today. This expansion may be linked to changing epidemiology, immune evasion or fitness under antimicrobial selection pressure, since many of the contemporary syphilis lineages we have characterized are resistant to macrolides. Global syphilis prevalence has been increasing. Sequencing and analysis of a global collection of 726 Treponema pallidum samples reveal globally circulating lineages linked to a rapid expansion occurring since the end of the twentieth century.
|
|
| 27. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
|
|
| 28. |
|
|
| 29. |
- Wiedeking, M., et al.
(författare)
-
Transition strengths and band terminations in 86Zr
- 2003
-
Ingår i: Physical Review C - Nuclear Physics. - 0556-2813. ; 67, s. 1-034320
-
Tidskriftsartikel (refereegranskat)abstract
- High angular momentum states in 86Zr were populated through the 58Ni(32S,4p) reaction at 135 MeV using the 88-In. Cyclotron at Lawrence Berkeley National Laboratory. Recoiling 86Zr nuclei were stopped in a thick Ta backing. Prompt multi-γ coincidences with evaporated charged particles were detected using the full array of GAMMASPHERE and the MICROBALL. Mean lifetimes of 36 levels in 86Zr were measured using the Doppler-shift attenuation method. Transition quadrupole moments Qt were found in the range of about 0.3-1.5 e b in the positive-parity bands. The negative-parity bands show Qt values from about 0.25 to 1.2 e b. In the yrast positive-parity band, a sharp drop in collectivity approaching the 30+ state supports the interpretation of band termination in this configuration. Decreasing Qt values approaching the 24+ and 27- states also provide an indication of terminating structures.
|
|
| 30. |
|
|
| 31. |
- Marcote, B., et al.
(författare)
-
A repeating fast radio burst source localized to a nearby spiral galaxy
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7789, s. 190-194
-
Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4–7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9–12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.
|
|
| 32. |
- Naidu, Sreus A G, et al.
(författare)
-
COVID-19 during Pregnancy and Postpartum : Antiviral Spectrum of Maternal Lactoferrin in Fetal and Neonatal Defense
- 2020
-
Ingår i: Journal of dietary supplements. - : Informa UK Limited. - 1939-0211 .- 1939-022X. ; , s. 1-37
-
Forskningsöversikt (refereegranskat)abstract
- As the COVID-19 pandemic intensified the global health crisis, the containment of SARS-CoV-2 infection in pregnancies, and the inherent risk of vertical transmission of virus from mother-to-fetus (or neonate) poses a major concern. Most COVID-19-Pregnancy patients showed mild to moderate COVID-19 pneumonia with no pregnancy loss and no congenital transmission of the virus; however, an increase in hypoxia-induced preterm deliveries was apparent. Also, the breastmilk of several mothers with COVID-19 tested negative for the virus. Taken together, the natural barrier function during pregnancy and postpartum seems to deter the SARS-CoV-2 transmission from mother-to-child. This clinical observation warrants to explore the maternal-fetal interface and identify the innate defense factors for prevention and control of COVID-19-Pregnancy. Lactoferrin (LF) is a potent antiviral iron-binding protein present in the maternal-fetal interface. In concert with immune co-factors, maternal-LF modulates chemokine release and lymphocyte migration and amplify host defense during pregnancy. LF levels during pregnancy may resolve hypertension via down-regulation of ACE2; consequently, may limit the membrane receptor access to SARS-CoV-2 for cellular entry. Furthermore, an LF-derived peptide (LRPVAA) has been shown to block ACE receptor activity in vitro. LF may also reduce viral docking and entry into host cells and limit the early phase of COVID-19 infection. An in-depth understanding of LF and other soluble mammalian milk-derived innate antiviral factors may provide insights to reduce co-morbidities and vertical transmission of SARS-CoV-2 infection and may lead to the development of effective nutraceutical supplements.
|
|
| 33. |
- Naidu, Sreus A.G., et al.
(författare)
-
COVID-19 during Pregnancy and Postpartum:: I) Pathobiology of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) at Maternal-Fetal Interface
- 2020
-
Ingår i: Journal of dietary supplements. - : Informa UK Limited. - 1939-0211 .- 1939-022X.
-
Forskningsöversikt (refereegranskat)abstract
- Coronavirus Disease 2019 (COVID-19) triggered by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has been declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Oxidative stress and its related metabolic syndromes are potential risk factors in the susceptibility to, and severity of COVID-19. In concert with the earliest reports of COVID-19, obstetricians started to diagnose and treat SARS-CoV-2 infections during pregnancy (“COVID-19-Pregnancy”). High metabolic demand to sustain normal fetal development increases the burden of oxidative stress in pregnancy. Intracellular redox changes intertwined with acute phase responses at the maternal-fetal interface could amplify during pregnancy. Interestingly, mother-to-fetus transmission of SARS-CoV-2 has not been detected in most of the COVID-19-Pregnancy cases. This relative absence of vertical transmission may be related to the presence of lactoferrin in the placenta, amniotic fluid, and lacteal secretions. However, the cytokine-storm induced during COVID-19-Pregnancy may cause severe inflammatory damage to the fetus, and if uncontrolled, may later result in autism spectrum-like disorders and brain development abnormalities in neonates. Considering this serious health threat to child growth and development, the prevention of COVID-19 during pregnancy should be considered a high priority. This review summarizes the intricate virulence factors of COVID-19 and elucidate its pathobiological spectrum during pregnancy and postpartum periods with a focus on the putative and complex roles of endogenous and exogenous lactoferrin in conferring immunological advantage to the host.
|
|
| 34. |
- Abudurexiti, A, et al.
(författare)
-
Taxonomy of the order Bunyavirales: update 2019
- 2019
-
Ingår i: Archives of virology. - : Springer Science and Business Media LLC. - 1432-8798 .- 0304-8608. ; 164:7, s. 1949-1965
-
Tidskriftsartikel (refereegranskat)
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Casares, L., et al.
(författare)
-
The synthetic triterpenoids CDDO-TFEA and CDDO-Me, but not CDDO, promote nuclear exclusion of BACH1 impairing its activity
- 2022
-
Ingår i: Redox Biology. - : Elsevier BV. - 2213-2317. ; 51
-
Tidskriftsartikel (refereegranskat)abstract
- The transcription factor BACH1 is a potential therapeutic target for a variety of chronic conditions linked to oxidative stress and inflammation, as well as cancer metastasis. However, only a few BACH1 degraders/inhibitors have been described. BACH1 is a transcriptional repressor of heme oxygenase 1 (HMOX1), which is positively regulated by transcription factor NRF2 and is highly inducible by derivatives of the synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO). Most of the therapeutic activities of these compounds are due to their anti-inflammatory and antioxidant properties, which are widely attributed to their ability to activate NRF2. However, with such a broad range of action, these compounds have other molecular targets that have not been fully identified and could also be of importance for their therapeutic profile. Herein we identified BACH1 as a target of two CDDO-derivatives (CDDO-Me and CDDO-TFEA), but not of CDDO. While both CDDO and CDDO-derivatives activate NRF2 similarly, only CDDO-Me and CDDO-TFEA inhibit BACH1, which explains the much higher potency of these CDDO-derivatives as HMOX1 inducers compared with unmodified CDDO. Notably, we demonstrate that CDDO-Me and CDDO-TFEA inhibit BACH1 via a novel mechanism that reduces BACH1 nuclear levels while accumulating its cytoplasmic form. In an in vitro model, both CDDO-derivatives impaired lung cancer cell invasion in a BACH1-dependent and NRF2-independent manner, while CDDO was inactive. Altogether, our study identifies CDDO-Me and CDDO-TFEA as dual KEAP1/BACH1 inhibitors, providing a rationale for further therapeutic uses of these drugs.
|
|
| 38. |
- Chouhan, Dimple, et al.
(författare)
-
Silkworm Silk Scaffolds Functionalized with Recombinant Spider Silk Containing a Fibronectin Motif Promotes Healing of Full-Thickness Burn Wounds
- 2019
-
Ingår i: ACS Biomaterials Science & Engineering. - : AMER CHEMICAL SOC. - 2373-9878. ; 5:9, s. 4634-4645
-
Tidskriftsartikel (refereegranskat)abstract
- Full-thickness cutaneous wounds, such as deep burns, are complex wounds that often require surgical interventions. Herein, we show the efficacy of acellular grafts that can be made available off-the-shelf at an affordable cost using silk biomaterials. Silkworm silk fibroin (SF), being a cost-effective and natural biopolymer, provides essential features required for the fabrication of three-dimensional constructs for wound-healing applications. We report the treatment of third-degree burn wounds using a freeze-dried microporous scaffold of Antheraea assama SF (AaSF) functionalized with a recombinant spider silk fusion protein FN-4RepCT (FN-4RC) that holds the fibronectin cell binding motif. In order to examine the healing efficiency of functionalized silk scaffolds, an in vivo burn rat model was used, and the scaffolds were implanted by a one-step grafting procedure. The aim of our work is to investigate the efficacy of the developed acellular silk grafts for treating full-thickness wounds as well as to examine the effect of recombinant spider silk coatings on the healing outcomes. Following 14-day treatment, AaSF scaffolds coated with FN-4RC demonstrated accelerated wound healing when compared to the uncoated counterpart, commercially used DuoDERM dressing patch, and untreated wounds. Histological assessments of wounds over time further confirmed that functionalized silk scaffolds promoted wound healing, showing vascularization and re-epithelialization in the initial phase. In addition, higher extent of tissue remodeling was affirmed by the gene expression study of collagen type I and type III, indicating advanced stage of healing by the silk treatments. Thus, the present study validates the potential of scaffolds of combined silkworm silk and FN-4RC for skin regeneration.
|
|
| 39. |
- Kumar Jeengar, Manish, et al.
(författare)
-
Local administration of 4-Thiouridine, a novel molecule with potent antiinflammatory properties, protects against experimental colitis and arthritis
- 2020
-
Ingår i: International Immunopharmacology. - : ELSEVIER. - 1567-5769 .- 1878-1705. ; 85
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies in a rat model of Sephadex induced lung inflammation showed that 4-Thiouridine (4SU), a thiol substituted nucleoside, was very effective in reducing edema, leukocyte influx and TNF levels in bronchoalvelolar lavage fluid. However, little is known about the factors and mechanisms underlying these effects. In the present study, we have used two separate mouse models of chronic inflammation, a model of dextran sulphate sodium (DSS) induced colitis and a model of antigen induced arthritis, to evaluate the anti-inflammatory effect of 4-thiouridine. We have analyzed a broad spectrum of inflammatory mediators in order to delineate the mechanisms behind a potential anti-inflammatory effect of 4SU. Colitis was induced in C57BL/6 mice by administration of 3.5% DSS in drinking water for 5 days and the potential anti-colitic effect of 4SU was assessed by monitoring the disease activity index (DAI), measurement of colon length and histopathological analysis of colon tissue. We analyzed tissue myeloperoxidase (MPO) activity, serum pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF), mRNA and protein expression of pro-inflammatory cytokines, COX-2, and NF-kappa B activity in colitis tissue. Intracolonic administration of 4SU (5 mg/kg & 10 mg/kg.) significantly inhibited MPO activity and reduced the levels of pro-inflammatory cytokines (IL-1 beta, IL-6 and TNF) as well as COX-2. Further, NF-kappa B activation was also blocked by attenuating the phosphorylation of IkB kinase (IKK alpha/beta) in DSS-induced colitis tissues. Arthritis was induced by intra-articular injection of mBSA in the knee of NMRI mice pre-immunized with mBSA and 4SU was administered locally by direct injection into the knee joint. The antiarthritic potential of 4SU was calculated by histopathological scores and histochemical analysis of joint tissue. Further, immunohistochemistry was used to study inflammatory cell infiltration and expression of cytokines and adhesion molecules in the synovium. Local administration of 50-100 mg/kg 4SU at the time of arthritis onset clearly prevented development of joint inflammation and efficiently inhibited synovial expression of CD18, local cytokine production and recruitment of leukocytes to the synovium. Taken together, our data clearly demonstrates a potent anti-inflammatory effect of 4SU in two experimental models. In conclusion 4SU could be a new promising candidate for therapeutic modulation of chronic inflammatory diseases like ulcerative colitis and arthritis.
|
|
| 40. |
- Kumar Jeengar, Manish, et al.
(författare)
-
Uridine Ameliorates Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice
- 2017
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Uridine, one of the four components that comprise RNA, has attracted attention as a novel therapeutic modulator of inflammation. However, very little is known about its effect on intestinal inflammation. The aim of the present study was to investigate the potential protective effect of intracolonic administered uridine against DSS induced colitis in male C57BL/6 mice. Intracolonic instillation of 3 doses of uridine 1 mg/Kg (lower dose), 5 mg/Kg (medium dose), and 10 mg/Kg (higher dose) in saline was performed daily. Uridine at medium and high dose significantly reduced the severity of colitis (DAI score) and alleviated the macroscopic and microscopic signs of the disease. The levels of proinflammatory cytokines IL-6, IL-1 beta and TNF in serum as well as mRNA expression in colon were significantly reduced in the uridine treated groups. Moreover, colon tissue myloperoxidase activities, protein expression of IL-6, TNF-alpha, COX-2, P-NFkB and P-Ikk-alpha beta in the colon tissues were significantly reduced in medium and high dose groups. These findings demonstrated that local administration of uridine alleviated experimental colitis in male C57BL/6 mice accompanied by the inhibition of neutrophil infiltration and NF-kappa B signaling. Thus, Uridine may be a promising candidate for future use in the treatment of inflammatory bowel disease.
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Nilsson, Carl Patrik, 1969-
(författare)
-
Attention to Advertising
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Attention to AdvertisingCarl Patrik Nilsson, Umeå School of Business, Umeå University SE-901 87 Umeå, SwedenAbstractIn advertising, capturing consumers’ attention is imperative. Yet, how attention to advertising works in a World Wide Web context has not been researched extensively. This area is the main focus of this research.The World Wide Web is an interactive medium which has characteristics that deviate from traditional media channels. Considering the unique properties of the World Wide Web it was deemed important to study how attention to advertising is affected by various contexts as well as attention getting techniques.The study was conducted in order to develop an understanding of how advertisements in different Web task environments are being attended to as well as how attention to advertisements varies between different attention getting techniques that are being used in Web advertising. Furthermore, a model which describes the relationship between context, attention getting techniques and attention to advertising was developed and tested. In connection to this it was tested whether click-through or click-rate is indeed an adequate method when measuring advertising effect and thereby to what extent the pay per click pricing strategy is appropriate.In order to address the research issues a theoretical framework was assembled. Nine hypotheses were formulated deriving from the framework. To test the hypotheses and the model, an experimental research design was employed. Three experiments were designed to study the hypotheses formulated. A total of 702 individual experiments were conducted.The conclusions from the study reveal that Web task environments indeed have an impact on attention to advertising. Increased complexity or a more difficult task environment demands more cognitive resources which in turn produces lower attention levels to the advertising stimulus. Reduced complexity, on the other hand, releases cognitive resources that can be spent elsewhere. Thus, a higher attention level to the advertising stimulus was recorded. This also confirmed the properties of the proposed model; namely that the permeability of a filtering mechanism is dependent on for instance level of goal orientation and complexity of the physical task environment i.e. the complexity of the Web site. The study revealed that attention getting techniques such as pop-up advertisements increase the attention to advertising. However, it was found that pop-up advertisements are effective, not mainly because of their abrupt presentation, but because of the distinct properties of the frame. It was found that the frame has a negative meaning for Web users and when the frame comes into the visual field it will attract their attention. At the same time attention will also be distributed towards the advertisement itself. This is recorded as an increase in attention towards the advertising message.The results show that the click-through measure is not an appropriate method when measuring advertising effect. The click-through measure may severely underestimate the advertising effect. Consequently, using click-through frequencies as a basis for pricing is inappropriate, unless the effects at play have been well understood and taken into consideration.Key words: Attention to advertising, attention getting techniques, Web advertising, Web environment, click-throughStudies in Business Administration, B series, No 60.ISSN 0346-8291, ISBN 91-7264-189-4Umeå School of Business - Sweden 2006
|
|
| 44. |
- Nitharwal, Ram G., et al.
(författare)
-
DNA binding activity of Helicobacter pylori DnaB helicase : the role of the N-terminal domain in modulating DNA binding activities
- 2012
-
Ingår i: The FEBS Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 279:2, s. 234-250
-
Tidskriftsartikel (refereegranskat)abstract
- Replicative helicases are major motor proteins essential for chromosomal DNA replication in prokaryotes. Usually hexameric in solution, their DNA binding property must have different roles at stages ranging from the loading onto a branched structure at initiation from the origin to the highly processive translocation during elongation. Here, we have analysed the DNA binding activity of Helicobacter pylori (Hp) replicative helicase, DnaB. The results indicate that while the C-terminal region is important for its DNA binding activity, the N-terminus appears to dampen the proteins affinity for DNA. The masking activity of the N-terminus does not require ATP or hexamerization of HpDnaB and can be overcome by deleting the N-terminus. It can also be neutralized by engaging the N-terminus in an interaction with a partner like the C-terminus of DnaG primase. The inhibitory effect of the N-terminus on DNA binding activity is consistent with the 3D homology model of HpDnaB. Electron microscopy of the HpDnaBssDNA complex showed that HpDnaB preferentially bound at the ends of linear ssDNA and translocated along the DNA in the presence of ATP. These results provide an insight into the stimulatory and inhibitory effects of different regions of HpDnaB on DNA binding activities that may be central to the loading and translocation functions of DnaB helicases.
|
|
| 45. |
- Pleunis, Z., et al.
(författare)
-
LOFAR Detection of 110-188MHz emission and frequency-dependent activity from FRB20180916B
- 2021
-
Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
-
Tidskriftsartikel (refereegranskat)abstract
- The object FRB 20180916B is a well-studied repeating fast radio burst source. Its proximity (∼150 Mpc), along with detailed studies of the bursts, has revealed many clues about its nature, including a 16.3 day periodicity in its activity. Here we report on the detection of 18 bursts using LOFAR at 110-188 MHz, by far the lowest-frequency detections of any FRB to date. Some bursts are seen down to the lowest observed frequency of 110 MHz, suggesting that their spectra extend even lower. These observations provide an order-of-magnitude stronger constraint on the optical depth due to freëCfree absorption in the source's local environment. The absence of circular polarization and nearly flat polarization angle curves are consistent with burst properties seen at 300-1700 MHz. Compared with higher frequencies, the larger burst widths (∼40-160 ms at 150 MHz) and lower linear polarization fractions are likely due to scattering. We find ∼2-3 rad m variations in the Faraday rotation measure that may be correlated with the activity cycle of the source. We compare the LOFAR burst arrival times to those of 38 previously published and 22 newly detected bursts from the uGMRT (200-450 MHz) and CHIME/FRB (400-800 MHz). Simultaneous observations show five CHIME/FRB bursts when no emission is detected by LOFAR. We find that the burst activity is systematically delayed toward lower frequencies by about 3 days from 600 to 150 MHz. We discuss these results in the context of a model in which FRB 20180916B is an interacting binary system featuring a neutron star and high-mass stellar companion.
|
|
| 46. |
- Scholz, P., et al.
(författare)
-
Simultaneous X-Ray and Radio Observations of the Repeating Fast Radio Burst FRB similar to 180916.J0158+65
- 2020
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 901:2
-
Tidskriftsartikel (refereegranskat)abstract
- We report on simultaneous radio and X-ray observations of the repeating fast radio burst source FRB 180916.J0158+65 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME), Effelsberg, and Deep Space Network (DSS-14 and DSS-63) radio telescopes and the Chandra X-ray Observatory. During 33 ks of Chandra observations, we detect no radio bursts in overlapping Effelsberg or Deep Space Network observations and a single burst during CHIME/FRB source transits. We detect no X-ray events in excess of the background during the Chandra observations. These non-detections imply a 5 sigma limit of <5 x 10(-10)erg cm(-2)for the 0.5-10 keV fluence of prompt emission at the time of the radio burst and 1.3 x 10(-9)erg cm(-2)at any time during the Chandra observations. Given the host-galaxy redshift of FRB 180916.J0158+65 (z similar to 0.034), these correspond to energy limits of <1.6 x 10(45)erg and <4 x 10(45)erg, respectively. We also place a 5 sigma limit of <8 x 10(-15)erg s(-1) cm(-2)on the 0.5-10 keV absorbed flux of a persistent source at the location of FRB 180916.J0158+65. This corresponds to a luminosity limit of <2 x 10(40)erg s(-1). Using an archival set of radio bursts from FRB 180916.J0158+65, we search for prompt gamma-ray emission in Fermi/GBM data but find no significant gamma-ray bursts, thereby placing a limit of 9 x 10(-9)erg cm(-2)on the 10-100 keV fluence. We also search Fermi/LAT data for periodic modulation of the gamma-ray brightness at the 16.35 days period of radio burst activity and detect no significant modulation. We compare these deep limits to the predictions of various fast radio burst models, but conclude that similar X-ray constraints on a closer fast radio burst source would be needed to strongly constrain theory.
|
|
| 47. |
- Zhu, Y. -G, et al.
(författare)
-
Editors’ foreword
- 2018
-
Ingår i: Environmental Arsenic in a ChangingWorld - 7th International Congress and Exhibition Arsenic in the Environment, 2018. - : CRC Press/Balkema. ; , s. xlv-xlvi
-
Konferensbidrag (refereegranskat)
|
|
