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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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2. |
- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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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.
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- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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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.
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6. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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7. |
- Adrian-Martinez, S., et al.
(författare)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Tidskriftsartikel (refereegranskat)abstract
- We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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8. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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15. |
- Taddei, C, et al.
(författare)
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Repositioning of the global epicentre of non-optimal cholesterol
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
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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.
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17. |
- Alvarez, E. M., et al.
(författare)
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The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019
- 2022
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Ingår i: Lancet Oncology. - : Elsevier BV. - 1470-2045. ; 23:1, s. 27-52
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Tidskriftsartikel (refereegranskat)abstract
- Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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21. |
- Reifarth, R., et al.
(författare)
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Nuclear astrophysics with radioactive ions at FAIR
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 665:1
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Konferensbidrag (refereegranskat)abstract
- The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process beta-decay chains. These nuclei are attributed to the p and rp process. For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections. The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
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22. |
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23. |
- 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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24. |
- 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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26. |
- Antonov, A. N., et al.
(författare)
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The electron-ion scattering experiment ELISe at the International Facility for Antiproton and Ion Research (FAIR)-A conceptual design study
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002 .- 0167-5087. ; 637:1, s. 60-76
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Tidskriftsartikel (refereegranskat)abstract
- The electron-ion scattering experiment ELISe is part of the installations envisaged at the new experimental storage ring at the International Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany. It offers an unique opportunity to use electrons as probe in investigations of the structure of exotic nuclei. The conceptual design and the scientific challenges of ELISe are presented. (C) 2011 Elsevier B.V. All rights reserved.
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27. |
- Zhou, Bin, et al.
(författare)
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Worldwide trends in diabetes since 1980: A pooled analysis of 751 population-based studies with 4.4 million participants
- 2016
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Ingår i: The Lancet. - : Elsevier B.V.. - 0140-6736 .- 1474-547X. ; 387:10027, s. 1513-1530
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are aff ecting the number of adults with diabetes.Methods: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.Findings: We used data from 751 studies including 4372000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-17.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target.Interpretation: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults aff ected, has increased faster in low-income and middle-income countries than in high-income countries.
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28. |
- Bianco, L., et al.
(författare)
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Discovery of W-157 and Os-161
- 2010
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 690:1, s. 15-18
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Tidskriftsartikel (refereegranskat)abstract
- The nuclides W-157 and Os-161 have been discovered ill reactions of Ni-58 ion beams with a Cd-106 target. The Os-161 alpha-decay energy and half-life were 6890 +/- 12 keV and 640 +/- 60 mu s. The daughter W-157 nuclei beta-decayed with a half-life of 275 +/- 40 ms, populating both low-lying alpha-decaying states in Ta-157, which is consistent with a 7/2(-) ground state in W-157. Fine structure observed in the alpha decay of Os-161 places the lowest excited state in W-157 with 1(pi) = 9/2(-) at 318 +/- 30 key. The branching ratio of 5.5(-2.2)(+3.1)% indicates that Os-161 also has a 7/2(-) ground state. Shell-model calculations analysing the effects of monopole shifts and a tensor force on the relative energies of 2f(7/2) and 1h(9/2) neutron states in N = 83 isotones are presented. (C) 2010 Elsevier B.V. All rights reserved.
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29. |
- Page, R. D., et al.
(författare)
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alpha decay of Re-159 and proton emission from Ta-155
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 75:6, s. 061302-
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Tidskriftsartikel (refereegranskat)abstract
- The alpha decay of Re-159 has been observed for the first time in reactions of 300 MeV Ni-58 ions with an isotopically enriched Cd-106 target. The Re-159 ions were separated in-flight using the RITU separator and implanted into the GREAT spectrometer. The alpha decay emanates from the proton-emitting pi h(11/2) state in Re-159 with an energy of E-alpha=6776 +/- 26 keV and a branching ratio of 7.5 +/- 3.5%. This alpha decay populates a state in the closed neutron shell nucleus Ta-155, which decays by emitting 1444 +/- 15 keV protons with a half-life of 2.9(-1.1)(+1.5) ms. These values are consistent with the emission of the proton from a pi h(11/2) orbital. These results fit in with the systematics of proton and alpha-particle separation energies in the region, but disagree with the previously reported decay properties of Ta-155.
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30. |
- Page, R. D., et al.
(författare)
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Probing single-particle structures beyond the proton drip line
- 2007
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Ingår i: Proton Emitting Nuclei and Related Topics. - : American Institute of Physics (AIP). - 9780735404755 ; , s. 137-142
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Konferensbidrag (refereegranskat)abstract
- Single-particle energies have been investigated in the closed neutron shell proton emitter 155Ta. The 155Ta nuclei were populated through the α decay of 159Re, which has been observed for the first time. The 159Re nuclei were produced in reactions of 300 MeV 58Ni ions with an isotopically enriched 106Cd target, separated in-flight using the RITU separator and implanted into the GREAT spectrometer. The 159Re α decay emanates from the proton-emitting πh11/2 state and populates a state in 155Ta which decays by the emission of a proton from a πh 11/2 orbital. The results fit in with the systematics of proton and α-particle separation energies in the region, but disagree with the previously reported decay properties of 155Ta.
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31. |
- Joss, D. T., et al.
(författare)
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Discovery of the proton emitting nucleus 159Re
- 2007
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Ingår i: Proton Emitting Nuclei and Related Topics. - : American Institute of Physics (AIP). - 9780735404755 ; , s. 28-33
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Konferensbidrag (refereegranskat)abstract
- The observation of the new nuclide 159Re provides important insights into the evolution of single-particle structure in heavy nuclei beyond the proton drip line. The nuclide 159Re was synthesised in the reaction 106Cd(58Ni, p4n) and identified via its proton radioactivity using the RITU gas-filled separator and the GREAT focal-plane spectrometer. Comparisons of the measured proton energy (Ep = 1805±20 keV) and decay half-life (t1/2 = 21±4 μs) with values calculated using the WKB method indicate that the proton is emitted from an h11/2 state. The implications of these results for future experimental investigations into even more proton unbound Re isotopes using in-flight separation techniques are considered.
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32. |
- Joss, D. T., et al.
(författare)
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Probing the limit of nuclear existence : Proton emission from Re-159
- 2006
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Ingår i: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 641:1, s. 34-37
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Tidskriftsartikel (refereegranskat)abstract
- The observation of the new nuclide Re-159(75)84 provides important insights into the evolution of single-particle structure and the mass surface in heavy nuclei beyond the proton drip line. This nuclide, 26 neutrons away from the nearest stable rhenium isotope, was synthesised in the reaction Cd-106(Ni-58, p4n) and identified via its proton radioactivity using the RITU gas-filled separator and the GREAT focal-plane spectrometer. Comparisons of the measured proton energy (E-p = 1805 +/- 20 keV) and decay half-life (t(1/2) = 21 +/- 4 mu s) with values calculated using the WKB method indicate that the proton is emitted from an h(11/2) state. The implications of these results for future experimental investigations into even more proton unbound nuclei using in-flight separation techniques are considered.
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35. |
- Al-Khalili, Lubna, et al.
(författare)
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Profiling of human myotubes reveals an intrinsic proteomic signature associated with type 2 diabetes
- 2014
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Ingår i: Translational Proteomics. - : Elsevier BV. - 2212-9634 .- 2212-9626. ; 2:1, s. 25-38
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Tidskriftsartikel (refereegranskat)abstract
- The development of insulin resistance and type 2 diabetes (T2D) involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT) healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE), the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7), glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2), and protein dynamics (heat shock protein, HSP, isoform B1 and 90A) showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.
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36. |
- Kennedy, S. A., et al.
(författare)
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Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
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37. |
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38. |
- Al-Khalili, L, et al.
(författare)
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Proteasome inhibition in skeletal muscle cells unmasks metabolic derangements in type 2 diabetes
- 2014
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 307:9, s. C774-C787
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.
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39. |
- Kalhori, S., et al.
(författare)
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Resonant ion-pair formation in electron collisions with rovibrationally cold H-3(+)
- 2004
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Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 69:2, s. 022713-
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Tidskriftsartikel (refereegranskat)abstract
- Experimental and theoretical cross sections for the resonant ion-pair formation (RIP) in electron collisions with rovibrationally cold H-3(+) ions are presented. Absolute cross sections for the RIP process producing H- ions are measured for center-of-mass energies between 2-20 eV using the CRYRING, heavy-ion storage ring. Theoretical cross sections are obtained using wave-packet propagation on both one- and two-dimensional models of relevant diabatic-potential energy surfaces and couplings of H-3(+) and H-3.
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40. |
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41. |
- Al-Khalili, A, et al.
(författare)
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Dissociative recombination cross section and branching ratios of protonated dimethyl disulfide and N-methylacetamide
- 2004
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 121:12, s. 5700-5708
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Tidskriftsartikel (refereegranskat)abstract
- Dimethyl disulfide (DMDS) and N-methylacetamide are two first choice model systems that represent the disulfide bridge bonding and the peptide bonding in proteins. These molecules are therefore suitable for investigation of the mechanisms involved when proteins fragment under electron capture dissociation (ECD). The dissociative recombination cross sections for both protonated DMDS and protonated N-methylacetamide were determined at electron energies ranging from 0.001 to 0.3 eV. Also, the branching ratios at 0 eV center-of-mass collision energy were determined. The present results give support for the indirect mechanism of ECD, where free hydrogen atoms produced in the initial fragmentation step induce further decomposition. We suggest that both indirect and direct dissociations play a role in ECD.
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42. |
- Cepeda, D., et al.
(författare)
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CDK-mediated activation of the SCFFBXO28 ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer
- 2013
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Ingår i: EMBO Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 5:7, s. 999-1018
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Tidskriftsartikel (refereegranskat)abstract
- SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors.
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43. |
- Fagerberg, Linn, et al.
(författare)
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Contribution of antibody-based protein profiling to the human chromosome-centric proteome project (C-HPP)
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:6, s. 2439-2448
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Tidskriftsartikel (refereegranskat)abstract
- A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas (www.proteinatlas.org).
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44. |
- Johansson, Camilla, et al.
(författare)
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Identification of Gene-Therapy Responsive Blood Biomarkers for Duchenne Muscular Dystrophy
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- IntroductionAssessing muscle dystrophin expression systemically is important for understanding the effect of dystrophin-restoring therapies in Duchenne muscular dystrophy (DMD). Many potential blood biomarkers have been identified in DMD patients which are either more or less abundant in blood samples compared to healthy individuals and that have been shown to change with disease progression or respond to pharmacological treatment. In this study, it was suggested that a panel of such blood biomarker candidates could be used to monitor dystrophin rescue in microdystrophin therapies. MethodsPlasma samples from mdx mice treated with the microdystrophin therapy SGT-001 were analysed with an antibody suspension bead array consisting of 87 antibodies targeting 83 proteins previously identified as biomarker candidates for DMD. Each sample was assayed at two different plasma dilutions to cover a broader concentration range. Median fluorescent intensities (MFI) for each antibody were correlated to dystrophin expression in muscle tissue, as measured by immunohistochemistry and Western blot. 13 targets were selected and validated in a DMD and Becker muscular dystrophy (BMD) longitudinal natural history cohort using a suspension bead array. Results10 proteins were found significantly elevated in untreated mdx mice compared to C57 wild-type mice and 10 were found to correlate with dystrophin expression (Spearman’s correlation, FDR < 0.05) upon gene transfer. Abundance of TTN, ADSSL1, LONP1, OTUD5, MYL3 as well as DMD protein were associated with dystrophin expression in BMD patients. Of these, MYL3 and ADSSL1 had different abundance in DMD compared to healthy individuals, and MYL3 also displayed different age trajectories between DMD and BMD patients. DiscussionThe ten proteins identified in mouse plasma are related to muscle contraction (ADSSL1, ASAH1, CA3, MYL3, TTN), microtubule formation (TPI1), and protein degradation (PSMA2, OTUD4, LONP1). Of these, MYL3 and ADSSL1 showed the most promise as a dystrophin monitoring biomarker in patient samples.
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45. |
- Koerkamp, M. G., et al.
(författare)
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Dissection of transient oxidative stress response in Saccharomyces cerevisiae by using DNA microarrays
- 2002
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 13:8, s. 2783-2794
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Tidskriftsartikel (refereegranskat)abstract
- Yeast cells were grown in glucose-limited chemostat cultures and forced to switch to a new carbon source, the fatty acid oleate. Alterations in gene expression were monitored using DNA microarrays combined with bioinformatics tools, among which was included the recently developed algorithm REDUCE. Immediately after the switch to oleate, a transient and very specific stress response was observed, followed by the up-regulation of genes encoding peroxisomal enzymes required for fatty acid metabolism. The stress response included up-regulation of genes coding for enzymes to keep thioredoxin and glutathione reduced, as well as enzymes required for the detoxification of reactive oxygen species. Among the genes coding for various isoenzymes involved in these processes, only a specific subset was expressed. Not the general stress transcription factors Msn2 and Msn4, but rather the specific factor Yap1p seemed to be the main regulator of the stress response. We ascribe the initiation of the oxidative stress response to a combination of poor redox flux and fatty acid-induced uncoupling of the respiratory chain during the metabolic reprogramming phase.
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46. |
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47. |
- Loh, Z-H, et al.
(författare)
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Observation of the fastest chemical processes in the radiolysis of water
- 2020
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Ingår i: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 367:6474, s. 179-182
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Tidskriftsartikel (refereegranskat)abstract
- Elementary processes associated with ionization of liquid water provide a framework for understanding radiation-matter interactions in chemistry and biology. Although numerous studies have been conducted on the dynamics of the hydrated electron, its partner arising from ionization of liquid water, H2O+, remains elusive. We used tunable femtosecond soft x-ray pulses from an x-ray free electron laser to reveal the dynamics of the valence hole created by strong-field ionization and to track the primary proton transfer reaction giving rise to the formation of OH. The isolated resonance associated with the valence hole (H2O+/OH) enabled straightforward detection. Molecular dynamics simulations revealed that the x-ray spectra are sensitive to structural dynamics at the ionization site. We found signatures of hydrated-electron dynamics in the x-ray spectrum.
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48. |
- Lourbakos, A., et al.
(författare)
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Evaluation of serum MMP-9 as predictive biomarker for antisense therapy in Duchenne
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Duchenne Muscular Dystrophy (DMD) is a severe muscle disorder caused by lack of dystrophin. Predictive biomarkers able to anticipate response to the therapeutic treatments aiming at dystrophin re-expression are lacking. The objective of this study is to investigate Matrix Metalloproteinase-9 (MMP-9) as predictive biomarker for Duchenne. Two natural history cohorts were studied including 168 longitudinal samples belonging to 66 patients. We further studied 1536 samples obtained from 3 independent clinical trials with drisapersen, an antisense oligonucleotide targeting exon 51: an open label study including 12 patients; a phase 3 randomized, double blind, placebo controlled study involving 186 patients; an open label extension study performed after the phase 3. Analysis of natural history cohorts showed elevated MMP-9 levels in patients and a significant increase over time in longitudinal samples. MMP-9 decreased in parallel to clinical stabilization in the 12 patients involved in the open label study. The phase 3 study and subsequent extension study clarified that the decrease in MMP-9 levels was not predictive of treatment response. These data do not support the inclusion of serum MMP-9 as predictive biomarker for DMD patients.
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49. |
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50. |
- Montaigne, Helen, et al.
(författare)
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Dissociative recombination of the thioformyl (HCS+) and carbonyl sulfide (OCS+) cations
- 2005
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 631:1, s. 653-659
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Tidskriftsartikel (refereegranskat)abstract
- Branching ratios and absolute cross sections have been measured for the dissociative recombination of HCS+ and OCS+ at the CRYRING ion storage ring. In the case of OCS+, the channel leading to CO + S ( 83%) dominates, whereas the other exoergic pathways leading to CS + O (14%) and C + SO (3%) are of lesser importance. In the case of HCS+, fracture of the C - S bond is predominant (81%), with the production of H + CS accounting for the remainder (19%). The cross section of the reaction could be fitted by the expressions sigma = 1.41 x 10(-15)E(eV)(-1.11) and 4.47 x 10(-16)E(eV) (-1.14) cm(2) for HCS+ and OCS+, respectively. The derived energy dependences of the thermal reaction rate coefficients can be fitted by k(T) 9.7 x 10(-7)(T/300)(-0.57) and 3.5 x 10(-7)(T/300)(-0.62) cm(3) s(-1) for HCS+ and OCS+, respectively. We use these data to perform model calculations on the HCS+/CS abundance ratio in dark clouds and find that the models using the UMIST and Ohio State University databases have even more difficulty in accounting for the large observed ratio.
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