| 1. |
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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- 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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| 4. |
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| 5. |
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| 6. |
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| 7. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 9. |
- Vos, Theo, et al.
(författare)
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Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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| 10. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 11. |
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| 12. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 13. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 14. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 15. |
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| 16. |
- Luo, Yifei, et al.
(författare)
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Technology Roadmap for Flexible Sensors
- 2023
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Ingår i: ACS Nano. - : American Chemical Society. - 1936-0851 .- 1936-086X. ; 17:6, s. 5211-5295
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Forskningsöversikt (refereegranskat)abstract
- Humans rely increasingly on sensors to address grand challenges and to improve quality of life in the era of digitalization and big data. For ubiquitous sensing, flexible sensors are developed to overcome the limitations of conventional rigid counterparts. Despite rapid advancement in bench-side research over the last decade, the market adoption of flexible sensors remains limited. To ease and to expedite their deployment, here, we identify bottlenecks hindering the maturation of flexible sensors and propose promising solutions. We first analyze challenges in achieving satisfactory sensing performance for real-world applications and then summarize issues in compatible sensor-biology interfaces, followed by brief discussions on powering and connecting sensor networks. Issues en route to commercialization and for sustainable growth of the sector are also analyzed, highlighting environmental concerns and emphasizing nontechnical issues such as business, regulatory, and ethical considerations. Additionally, we look at future intelligent flexible sensors. In proposing a comprehensive roadmap, we hope to steer research efforts towards common goals and to guide coordinated development strategies from disparate communities. Through such collaborative efforts, scientific breakthroughs can be made sooner and capitalized for the betterment of humanity.
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| 17. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 18. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 19. |
- Fu, Jianjie, et al.
(författare)
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Elevated levels of perfluoroalkyl acids in family members of occupationally exposed workers : the importance of dust transfer
- 2015
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The exposure pathways of perfluoroalkyl acids (PFAAs) to humans are still not clear because of the complex living environment, and few studies have simultaneously investigated the bioaccumulative behaviour of different PFAAs in humans. In this study, serum, dust, duplicate diet, and other matrices were collected around a manufacturing plant in China, and homologous series of PFAAs were analysed. PFAA levels in dust and serum of local residents in this area were considerably higher than those in non-polluted area. Although dietary intake was the major exposure pathway in the present study, dust ingestion played an important role in this case. Serum PFAAs in local residents was significantly correlated with dust PFAAs levels in their living or working microenvironment. Serum PFAAs and dust PFAAs were significantly higher in family members of occupational workers (FM) than in ordinary residents (OR) (p<0.01). After a careful analysis of the PFAAs exposure pathway, a potential pathway in addition to direct dust ingestion was suggested: PFAAs might transferred from occupational worker's clothes to dinners via cooking processes. The bioaccumulative potential of PFHxS and PFOS were higher than other PFAAs, which suggested a substantial difference between the bioaccumulative ability of perfluorinated sulfonic acids and perfluorinated carboxylic acids.
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| 20. |
- Gao, Yan, et al.
(författare)
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Differential accumulation and elimination behavior of perfluoroalkyl acid isomers in occupational workers in a manufactory in China
- 2015
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:11, s. 6953-6962
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Tidskriftsartikel (refereegranskat)abstract
- In this study, serum and urine samples were collected from 36 occupational workers in a fluorochemical manufacturing plant in China from 2008 to 2012 to evaluate the body burden and possible elimination of linear and branched perfluoroalkyl acids (PFAAs). Indoor dust, total suspended particles (TSP), diet, and drinking water samples were also collected to trace the occupational exposure pathway to PFAA isomers. The geometric mean concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) isomers in the serum were 1386, 371, and 863 ng mL(-1), respectively. The linear isomer of PFOS, PFOA, and PFHxS was the most predominant PFAA in the serum, with mean proportions of 63.3, 91.1, and 92.7% respectively, which were higher than the proportions in urine. The most important exposure routes to PFAA isomers in the occupational workers were considered to be the intake of indoor dust and TSP. A renal clearance estimation indicated that branched PFAA isomers had a higher renal clearance rate than did the corresponding linear isomers. Molecular docking modeling implied that linear PFOS (n-PFOS) had a stronger interaction with human serum albumin (HSA) than branched isomers did, which could decrease the proportion of n-PFOS in the blood of humans via the transport of HSA.
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| 21. |
- Hu, Hai-Xi, et al.
(författare)
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Structural insights into HetR-PatS interaction involved in cyanobacterial pattern formation
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- The one-dimensional pattern of heterocyst in the model cyanobacterium Anabaena sp. PCC 7120 is coordinated by the transcription factor HetR and PatS peptide. Here we report the complex structures of HetR binding to DNA, and its hood domain (HetR(Hood)) binding to a PatS-derived hexapeptide (PatS6) at 2.80 and 2.10 angstrom, respectively. The intertwined HetR dimer possesses a couple of novel HTH motifs, each of which consists of two canonical alpha-helices in the DNA-binding domain and an auxiliary alpha-helix from the flap domain of the neighboring subunit. Two PatS6 peptides bind to the lateral clefts of HetR(Hood), and trigger significant conformational changes of the flap domain, resulting in dissociation of the auxiliary alpha-helix and eventually release of HetR from the DNA major grove. These findings provide the structural insights into a prokaryotic example of Turing model.
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| 22. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 23. |
- Jin, Rong, et al.
(författare)
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Profiles, sources and potential exposures of parent, chlorinated and brominated polycyclic aromatic hydrocarbons in haze associated atmosphere
- 2017
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 593-594, s. 390-398
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Tidskriftsartikel (refereegranskat)abstract
- Profiles, sources and potential exposures of chlorinated and brominated polycyclic aromatic hydrocarbons (ClPAHs and BrPAHs) in haze associated atmosphere remain unclear. Haze events happened frequently during heating period in Beijing provided a typical urban context to investigate the concentrations, profiles, sources and potential exposures of ClPAHs, BrPAHs and their non-halogenated parent compounds (PAHs) in air samples. Average concentrations of PAHs, ClPAHs and BrPAHs during heating periods (with more frequent haze events) were about 3-9 times higher than during non-heating periods. Concentrations of particulate matter (PM)-associated ClPAHs and BrPAHs were higher in heating period than in non-heating period, while for gas-associated ClPAHs and BrPAHs, this distinction was not significant. Congener patterns and congener profiles indicated that with increasing coal combustion during the heating period, concentrations of PAHs and ClPAHs in air were elevated in comparison to the non-heating period. Inhalation of PM-associated PAHs, ClPAHs and BrPAHs accounted for higher exposure than inhalation of gas phase and dermal contact of both gas phase and particulate phase. In this study we found that the particulate phase is the dominant exposure pathway of atmospheric PAHs, ClPAHs and BrPAHs during haze days, which is different from previous studies.
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| 24. |
- Qian, Liangxin, et al.
(författare)
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Multi-Dimensional Polarized Modulation for Land Mobile Satellite Communications
- 2021
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Ingår i: IEEE Transactions on Cognitive Communications and Networking. - : Institute of Electrical and Electronics Engineers (IEEE). - 2332-7731. ; 7:2, s. 383-397
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Tidskriftsartikel (refereegranskat)abstract
- In this article, a novel multiple-input multiple-out (MIMO) transmission scheme, called generalized polarized enhanced spatial modulation (GPESM), is proposed for dual-polarized land mobile satellite (LMS) communications. We first introduce the enhanced spatial modulation (ESM) technique for dual-polarized LMS communications, in which polarization dimension, spatial dimension and multiple signal constellations are used to transmit information and obtain substantial performance gain. Meanwhile, the theoretical upper bound for the average bit error probability (ABEP) of the proposed GPESM scheme is derived. In order to further improve the reliability of the system, we also propose two novel power allocation (PA) algorithms for GPESM system, which are the optimization-driven approximated max-min distance (AMMD)-based PA algorithm and the data-driven deep neural network (DNN)-based PA algorithm. To achieve an enhanced spatial diversity gain, we consider to apply a reconfigurable intelligent surface (RIS) to the GPESM system as a relay to assist in transmitting information. In this way, the user can receive the information transmitted by the satellite on one hand, and the information sent by the satellite via the RIS relay on the other hand. We also extend the above-mentioned two PA algorithms to the RIS-assisted GPESM systems. Our simulation results show that the RIS-assisted GPESM systems are capable of obtaining high bit error rate (BER) performance gain (up to 10 dB) compared to the standard GPESM system and two PA algorithms can further improve the performance to the systems.
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| 25. |
- Qu, Yanhua, 1974-, et al.
(författare)
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The evolution of ancestral and species-specific adaptations in snowfinches at the Qinghai-Tibet Plateau
- 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. ; 10.1073/pnas.2012398118:13, s. e2012398118-e2012398118
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Tidskriftsartikel (refereegranskat)abstract
- Species in a shared environment tend to evolve similar adaptations under the influence of their phylogenetic context. Using snowfinches, a monophyletic group of passerine birds (Passeridae), we study the relative roles of ancestral and species-specific adaptations to an extreme high-elevation environment, the Qinghai–Tibet Plateau. Our ancestral trait reconstruction shows that the ancestral snowfinch occupied high elevations and had a larger body mass than most nonsnowfinches in Passeridae. Subsequently, this phenotypic adaptation diversified in the descendant species. By comparing high-quality genomes from representatives of the three phylogenetic lineages, we find that about 95% of genes under positive selection in the descendant species are different from those in the ancestor. Consistently, the biological functions enriched for these species differ from those of their ancestor to various degrees (semantic similarity values ranging from 0.27 to 0.5), suggesting that the three descendant species have evolved divergently from the initial adaptation in their common ancestor. Using a functional assay to a highly selective gene, DTL, we demonstrate that the nonsynonymous substitutions in the ancestor and descendant species have improved the repair capacity of ultraviolet-induced DNA damage. The repair kinetics of the DTL gene shows a twofold to fourfold variation across the ancestor and the descendants. Collectively, this study reveals an exceptional case of adaptive evolution to high-elevation environments, an evolutionary process with an initial adaptation in the common ancestor followed by adaptive diversification of the descendant species.
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| 26. |
- Sun, Zhendong, et al.
(författare)
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4-Hexylphenol influences adipogenic differentiation and hepatic lipid accumulation in vitro
- 2021
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 268:Part A
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Tidskriftsartikel (refereegranskat)abstract
- Finding the potential environmental obesogens is crucial to explain the prevalence of obesity and the related pathologies. Increasing evidence has showed that many chemicals with endocrine disrupting effects can disturb lipid metabolism. Whether 4-hexylphenol (4-HP), a widely-used surfactant and a potential endocrine disrupting chemical (EDC), is associated to influence adipogenesis and hepatic lipid accumulation remained to be elucidated. In this study, both the 3T3-L1 differentiation model and oleic acid (OA)-treated HepG2 cells were used to investigate the effects of 4-HP on lipid metabolism, and the underlying estrogen receptor (ER)-involved mechanism was explored using MVLN assay, molecular docking simulation and the antagonist test. The results based on lipid droplet staining and triglyceride accumulation assay showed that 4-HP treatment promoted the adipogenic differentiation of 3T3-L1 cells and increased hepatic cellular OA accumulation in exposure concentration-dependent manners. The study on the elaborated transcription networks indicated that 4-HP activated peroxisome proliferator-activated receptor γ (PPARγ) as well as the subsequent adipogenic gene program in 3T3-L1 cells. This chemical also induced the increase of OA uptake and decreases of de novo lipogenesis and fatty acid oxidation in HepG2 cells. The agonistic activity of 4-HP in triggering ER-mediated pathway was shown to correlate with its perturbation in lipid metabolism, as evidenced by the enhanced development of mature lipid-laden adipocytes and suppression of excessive hepatic lipid accumulation upon its co-treatment with ER antagonist. Altogether, these findings provide new insights into the potential health impacts of 4-HP exposure as it may relate to obesity and nonalcoholic fatty liver disease.
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| 27. |
- Sun, Zhendong, et al.
(författare)
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Perturbation of 3-tert-butyl-4-hydroxyanisole in adipogenesis of male mice with normal and high fat diets
- 2020
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 703
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Tidskriftsartikel (refereegranskat)abstract
- As one of the widely used anthropogenic food additives, 3-tert-butyl-4-hydroxyanisole (3-BHA) has been found to perturb adipogenesis in vitro and induce lipid accumulation in some strains of oleaginous microalgae. The impact of this chemical on adipocyte development and lipid metabolism in mammals remains to be elucidated. In this study, we performed 18-week oral administration of 3-BHA to male C57BL/6J mice with normal diet (ND) or high-fat diet (HFD) and investigated its impacts on adipogenesis and lipid accumulation in vivo. The results indicated that long-term exposure to 3-BHA impacted the mouse body weight gain, white adipose tissue accumulation, and plasma lipids through transcriptional regulation of adipogenesis, lipid metabolism, and adipocyte endocrine function, while glucose metabolism and insulin sensitivity remained unaffected. HFD-fed mice responded to 3-BHA stimulation differently from ND-fed animals, suggesting potential risks for the human burden of 3-BHA in lean and obese subjects. The findings herein validate 3-BHA as an environmental obesogen, and more caution is recommended for its authorized use as a food antioxidant against lipid rancidity.
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| 28. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 29. |
- Wang, Pu, et al.
(författare)
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Sources and environmental behaviors of Dechlorane Plus and related compounds : A review
- 2016
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Ingår i: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 88, s. 206-220
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Forskningsöversikt (refereegranskat)abstract
- Although Dechlorane Plus (DP) has been used as a polychlorinated flame retardant for almost half a century, its detection in the environment was not reported until 2006. The subsequent intensive research has confirmed its global ubiquity. A few reviews have presented the properties, analytical methods and environmental occurrence of DP and related compounds in the past several years. The present review emphasizes on the environmental behavior of DP isomers which is assessed by the variation of the isomer ratio of DP in various matrices. Other aspects including the analytical methods, emission sources, general environmental occurrence and bioaccumulation of DP are also summarized.In this review, three typical emission sources in the environment are categorized after introducing the measurement method of DP. The temporal-spatial distribution is then evaluated at the global scale, which provides an integrated representation of the environmental occurrence of DP and potential impact on the human health and ecosystems. The variations of DP isomer ratio in various matrices reinforce its source related distribution and their stereoselective bioaccumulation. Thereafter, DP related compounds and dechlorinated analogs are briefly summarized in regards to their occurrence in various matrices, suggesting their ubiquity in the environment and bioavailability. Further studies are required to better assess the exposures and toxicological effects of DP and its analogs. A special concern is the serious contamination in e-waste recycling areas in developing countries, where long-term monitoring data on the association of DP exposure and adverse effects to human health and ecosystems is urgently needed.
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| 30. |
- Wang, Yawei, et al.
(författare)
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Distribution of perfluorooctane sulfonate and other perfluorochemicals in the ambient environment around a manufacturing facility in China
- 2010
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 44:21, s. 8062-8067
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Tidskriftsartikel (refereegranskat)abstract
- Perfluorinated compounds (PFCs) can be released to the surrounding environment during manufacturing and usage of PFC containing products, which are considered as main direct sources of PFCs in the environment. This study evaluates the release of perfluorooctane sulfonate (PFOS) and other PFCs to the ambient environment around a manufacturing plant. Among the nine PFCs analyzed, only PFOS, perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) were found in dust, water, soil, and chicken eggs. Very high concentrations of PFOS and PFOA were found in dust from the production storage, raw material stock room, and sulfonation workshop in the manufacturing facility, with the highest value at 4962 μg/g (dry weight) for PFOS and 160 μg/g for PFOA. A decreasing trend of the three PFCs concentrations in soils, water, and chicken eggs with increasing distance from the plant was found, indicating the production site to be the primary source of PFCs in this region. Risk quotients (RQs) assessment for surface water >500 m away from the plant were less than unity. Risk assessment of PFOS using predicted no-effect concentration (PNEC, 3.23 ng/g on a logarithmic scale) indicated no immediate ecological risk of a reduction in offspring survival. PFOS concentrations in most egg samples did not exceed the benchmark concentration derived in setting a reference dose for noncancer health effects (0.025 μg/(kgxd)).
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| 31. |
- Watts, Nick, et al.
(författare)
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Health and climate change : policy responses to protect public health
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10006, s. 1861-1914
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Forskningsöversikt (refereegranskat)abstract
- The 2015 Lancet Commission on Health and Climate Change has been formed to map out the impacts of climate change, and the necessary policy responses, in order to ensure the highest attainable standards of health for populations worldwide. This Commission is multidisciplinary and international in nature, with strong collaboration between academic centres in Europe and China. The central finding from the Commission's work is that tackling climate change could be the greatest global health opportunity of the 21st century. The key messages from the Commission are summarised below, accompanied by ten underlying recommendations to accelerate action in the next 5 years.
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| 32. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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| 33. |
- Xie, Wenjing, et al.
(författare)
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Unexpected Dioxin Formation During Digestion of Soil with Oxidizing Acids
- 2023
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Ingår i: Environmental Science and Technology. - : AMER CHEMICAL SOC. - 0013-936X .- 1520-5851. ; 57:39, s. 14717-14725
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Tidskriftsartikel (refereegranskat)abstract
- Dioxins, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs), are among the most toxic unintentionally produced persistent organic pollutants, and their emission is of great concern. Herein, we discovered abundant dioxin formation in soil and various organic carbon-containing matrices after digestion with aqua regia. Sigma 17PCDD/Fs concentrations were in the range of 66.6-142,834 pg/g dw (5.6-17,021 pg WHO2005-TEQ/g dw) in 19 soil samples after digestion with aqua regia for 6 h. Sigma 17PCDD/Fs concentration was significantly and positively correlated with soil organic carbon content (R-2 = 0.89; p < 0.01). Compared with cellulose and lignin, humic acid served as an important organic matter component that was converted to PCDD/Fs during soil digestion. Strong oxidation and production of reactive chlorine by aqua regia may be the key factors in the formation of PCDD/Fs. The yearly emission of PCDD/Fs due to digestion with strong acids by the inspection and testing industry was estimated to be 83.8 g TEQ in China in 2021 based on the highest level, which was similar to 0.9% of the total dioxin inventory in China. Great attention should be paid to unexpected dioxin formation during digestion processes considering the potential risk of release from laboratories and enterprises.
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