| 51. |
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| 52. |
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| 53. |
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| 54. |
- Bertolotto, Corine, et al.
(author)
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A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 480:7375, s. 94-98
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Journal article (peer-reviewed)abstract
- So far, no common environmental and/or phenotypic factor has been associated with melanoma and renal cell carcinoma (RCC). The known risk factors for melanoma include sun exposure, pigmentation and nevus phenotypes(1); risk factors associated with RCC include smoking, obesity and hypertension(2). A recent study of coexisting melanoma and RCC in the same patients supports a genetic predisposition underlying the association between these two cancers(3). The microphthalmia-associated transcription factor (MITF) has been proposed to act as a melanoma oncogene(4); it also stimulates the transcription of hypoxia inducible factor(5) (HIF1A), the pathway of which is targeted by kidney cancer susceptibility genes(6). We therefore proposed that MITF might have a role in conferring a genetic predisposition to co-occurring melanoma and RCC. Here we identify a germline missense substitution in MITF (Mi-E318K) that occurred at a significantly higher frequency in genetically enriched patients affected with melanoma, RCC or both cancers, when compared with controls. Overall, Mi-E318K carriers had a higher than fivefold increased risk of developing melanoma, RCC or both cancers. Codon 318 is located in a small-ubiquitin-like modifier (SUMO) consensus site (Psi KXE) and Mi-E318K severely impaired SUMOylation of MITF. Mi-E318K enhanced MITF protein binding to the HIF1A promoter and increased its transcriptional activity compared to wild-type MITF. Further, we observed a global increase in Mi-E318K occupied loci. In an RCC cell line, gene expression profiling identified a Mi-E318K signature related to cell growth, proliferation and inflammation. Lastly, the mutant protein enhanced melanocytic and renal cell clonogenicity, migration and invasion, consistent with a gain-of-function role in tumorigenesis. Our data provide insights into the link between SUMOylation, transcription and cancer.
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| 55. |
- Betsholtz, Christer
(author)
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Double function at the blood-brain barrier
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 509:7501, s. 432-433
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Journal article (other academic/artistic)
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| 56. |
- Betsholtz, Christer
(author)
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Transcriptional control of endothelial energy
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 529:7585, s. 160-161
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Journal article (other academic/artistic)
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| 57. |
- Beznosov, Pavel A., et al.
(author)
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Morphology of the earliest reconstructable tetrapod Parmastega aelidae
- 2019
-
In: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 574:7779, s. 527-531
-
Journal article (peer-reviewed)abstract
- The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments(1-15). The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles(2,4,16-34). All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments(5,10), and nearly 30 million years younger than the oldest known tetrapod footprints(35). Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods.
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| 58. |
- Bixby, H., et al.
(author)
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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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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
-
Journal article (peer-reviewed)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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| 59. |
- Bjerkeli, Per, 1977, et al.
(author)
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Resolved images of a protostellar outflow driven by an extended disk wind.
- 2016
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 540:7633, s. 406-409
-
Journal article (peer-reviewed)abstract
- Young stars are associated with prominent outflows of molecular gas. The ejection of gas is believed to remove angular momentum from the protostellar system, permitting young stars to grow by the accretion of material from the protostellar disk. The underlying mechanism for outflow ejection is not yet understood, but is believed to be closely linked to the protostellar disk. Various models have been proposed to explain the outflows, differing mainly in the region where acceleration of material takes place: close to the protostar itself ('X-wind', or stellar wind), in a larger region throughout the protostellar disk (disk wind), or at the interface between the two. Outflow launching regions have so far been probed only by indirect extrapolation because of observational limits. Here we report resolved images of carbon monoxide towards the outflow associated with the TMC1A protostellar system. These data show that gas is ejected from a region extending up to a radial distance of 25 astronomical units from the central protostar, and that angular momentum is removed from an extended region of the disk. This demonstrates that the outflowing gas is launched by an extended disk wind from a Keplerian disk.
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| 60. |
- Björkman, Anne, 1981, et al.
(author)
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Plant functional trait change across a warming tundra biome
- 2018
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
-
Journal article (peer-reviewed)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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