| 1071. |
- Takala, Heikki, et al.
(författare)
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Signal amplification and transduction in phytochrome photosensors
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 509:7499, s. 245-248
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Tidskriftsartikel (refereegranskat)abstract
- Sensory proteins must relay structural signals from the sensory site over large distances to regulatory output domains. Phytochromes are a major family of red-light-sensing kinases that control diverse cellular functions in plants, bacteria and fungi(1-9). Bacterial phytochromes consist of a photosensory core and a carboxy-terminal regulatory domain(10,11). Structures of photosensory cores are reported in the resting state(12-18) and conformational responses to light activation have been proposed in the vicinity of the chromophore(19-23). However, the structure of the signalling state and the mechanism of downstream signal relay through the photosensory core remain elusive. Here we report crystal and solution structures of the resting and activated states of the photosensory core of the bacteriophytochrome from Deinococcus radiodurans. The structures show an open and closed form of the dimeric protein for the activated and resting states, respectively. This nanometre-scale rearrangement is controlled by refolding of an evolutionarily conserved 'tongue', which is in contact with the chromophore. The findings reveal an unusual mechanism in which atomic-scale conformational changes around the chromophore are first amplified into ana angstrom-scale distance change in the tongue, and further grow into a nanometre-scale conformational signal. The structural mechanism is a blueprint for understanding how phytochromes connect to the cellular signalling network.
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| 1072. |
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| 1073. |
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| 1074. |
- Tammela, Tuomas, et al.
(författare)
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Blocking VEGFR-3 suppresses angiogenic sprouting and vascular network formation.
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 454:7204, s. 656-60
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is a key process in several pathological conditions, including tumour growth and age-related macular degeneration. Vascular endothelial growth factors (VEGFs) stimulate angiogenesis and lymphangiogenesis by activating VEGF receptor (VEGFR) tyrosine kinases in endothelial cells. VEGFR-3 (also known as FLT-4) is present in all endothelia during development, and in the adult it becomes restricted to the lymphatic endothelium. However, VEGFR-3 is upregulated in the microvasculature of tumours and wounds. Here we demonstrate that VEGFR-3 is highly expressed in angiogenic sprouts, and genetic targeting of VEGFR-3 or blocking of VEGFR-3 signalling with monoclonal antibodies results in decreased sprouting, vascular density, vessel branching and endothelial cell proliferation in mouse angiogenesis models. Stimulation of VEGFR-3 augmented VEGF-induced angiogenesis and sustained angiogenesis even in the presence of VEGFR-2 (also known as KDR or FLK-1) inhibitors, whereas antibodies against VEGFR-3 and VEGFR-2 in combination resulted in additive inhibition of angiogenesis and tumour growth. Furthermore, genetic or pharmacological disruption of the Notch signalling pathway led to widespread endothelial VEGFR-3 expression and excessive sprouting, which was inhibited by blocking VEGFR-3 signals. Our results implicate VEGFR-3 as a regulator of vascular network formation. Targeting VEGFR-3 may provide additional efficacy for anti-angiogenic therapies, especially towards vessels that are resistant to VEGF or VEGFR-2 inhibitors.
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| 1075. |
- Tanvir, N. R., et al.
(författare)
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A γ-ray burst at a redshift of z~8.2
- 2009
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 461, s. 1254-1257
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Tidskriftsartikel (refereegranskat)abstract
- Long-duration γ-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z>20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-α emitting galaxy. Here we report that GRB090423 lies at a redshift of z~8.2, implying that massive stars were being produced and dying as GRBs ~630Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.
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| 1076. |
- Tao, Feng, et al.
(författare)
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Microbial carbon use efficiency promotes global soil carbon storage
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 981-985
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Tidskriftsartikel (refereegranskat)abstract
- Soils store more carbon than other terrestrial ecosystems. How soil organic carbon (SOC) forms and persists remains uncertain, which makes it challenging to understand how it will respond to climatic change. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.
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| 1077. |
- Tavares, Julia, et al.
(författare)
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Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests
- 2023
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7959, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forests face increasing climate risk(1,2), yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, ?(50)) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk(3-5), little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters ?(50) and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both ?(50) and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM(50 )forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon(6,7), with strong implications for the Amazon carbon sink.
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| 1078. |
- Tedeschi, Antonio, et al.
(författare)
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Wapl is an essential regulator of chromatin structure and chromosome segregation
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 564-568
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Tidskriftsartikel (refereegranskat)abstract
- Mammalian genomes contain several billion base pairs of DNA that are packaged in chromatin fibres. At selected gene loci, cohesin complexes have been proposed to arrange these fibres into higher-order structures, but how important this function is for determining overall chromosome architecture and how the process is regulated are not well understood. Using conditional mutagenesis in the mouse, here we show that depletion of the cohesin-associated protein Wapl stably locks cohesin on DNA, leads to clustering of cohesin in axial structures, and causes chromatin condensation in interphase chromosomes. These findings reveal that the stability of cohesin-DNA interactions is an important determinant of chromatin structure, and indicate that cohesin has an architectural role in interphase chromosome territories. Furthermore, we show that regulation of cohesin-DNA interactions by Wapl is important for embryonic development, expression of genes such as c-myc (also known as Myc), and cell cycle progression. In mitosis, Wapl-mediated release of cohesin from DNA is essential for proper chromosome segregation and protects cohesin from cleavage by the protease separase, thus enabling mitotic exit in the presence of functional cohesin complexes.
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| 1079. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 1080. |
- Theopold, Ulrich
(författare)
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A bad boy comes good
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461, s. 486-487
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Forskningsöversikt (populärvet., debatt m.m.)
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