| 1861. |
- Christiansen, J. R., et al.
(författare)
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Deficiency of Isoprenylcysteine Carboxyl Methyltransferase (ICMT) Leads to Progressive Loss of Photoreceptor Function
- 2016
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Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 36:18, s. 5107-5114
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Tidskriftsartikel (refereegranskat)abstract
- Retinal neurons use multiple strategies to fine-tune visual signal transduction, including post-translational modifications of proteins, such as addition of an isoprenyl lipid to a carboxyl-terminal cysteine in proteins that terminate with a "CAAX motif." We previously showed that RAS converting enzyme 1 (RCE1)-mediated processing of isoprenylated proteins is required for photoreceptor maintenance and function. However, it is not yet known whether the requirement for the RCE1-mediated protein processing is related to the absence of the endoproteolytic processing step, the absence of the subsequent methylation step by isoprenylcysteine methyltransferase (ICMT), or both. To approach this issue and to understand the significance of protein methylation, we generated mice lacking Icmt expression in the retina. In the absence of Icmt expression, rod and cone light-mediated responses diminished progressively. Lack of ICMT-mediated methylation led to defective association of isoprenylated transducin and cone phosphodiesterase 6 (PDE6 alpha') with photoreceptor membranes and resulted in decreased levels of transducin, PDE6 alpha', and cone G-protein coupled receptor kinase-1 (GRK1). In contrast to our earlier findings with retina-specific Rce1 knock-out mice, rod PDE6 in Icmt-deficient mice trafficked normally to the photoreceptor outer segment, suggesting that the failure to remove the - AAX is responsible for blocking the movement of PDE6 to the outer segment. Our findings demonstrate that carboxyl methylation of isoprenylated proteins is crucial for maintenance of photoreceptor function.
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| 1862. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 1863. |
- Chrysafi, Anna, et al.
(författare)
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Quantifying Earth system interactions for sustainable food production via expert elicitation
- 2022
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Ingår i: Nature Sustainability. - : Springer Science and Business Media LLC. - 2398-9629. ; 5:10, s. 830-842
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Tidskriftsartikel (refereegranskat)abstract
- Several safe boundaries of critical Earth system processes have already been crossed due to human perturbations; not accounting for their interactions may further narrow the safe operating space for humanity. Using expert knowledge elicitation, we explored interactions among seven variables representing Earth system processes relevant to food production, identifying many interactions little explored in Earth system literature. We found that green water and land system change affect other Earth system processes strongly, while land, freshwater and ocean components of biosphere integrity are the most impacted by other Earth system processes, most notably blue water and biogeochemical flows. We also mapped a complex network of mechanisms mediating these interactions and created a future research prioritization scheme based on interaction strengths and existing knowledge gaps. Our study improves the understanding of Earth system interactions, with sustainability implications including improved Earth system modelling and more explicit biophysical limits for future food production.
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| 1864. |
- Chuvilin, E., et al.
(författare)
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In-situ temperatures and thermal properties of the East Siberian Arctic shelf sediments : Key input for understanding the dynamics of subsea permafrost
- 2022
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Ingår i: Marine and Petroleum Geology. - : Elsevier BV. - 0264-8172 .- 1873-4073. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- Significant reserves of methane (CH4) are held in the Arctic shelf, but the release of CH4 to the overlying ocean and, subsequently, to the atmosphere has been believed to be restricted by impermeable subsea permafrost, which has sealed the upper sediment layers for thousands of years. Our studies demonstrate progressive degradation of subsea permafrost which controls the scales of CH4 release from the sediment into the water-atmospheric system. Thus, new knowledge about the thermal state of subsea permafrost is crucial for better understanding of the permafrost -hydrate system and associated CH4 release from the East Siberian Arctic Shelf (ESAS) – the broadest and shallowest shelf in the World Ocean, which contains about 80% of subsea permafrost and giant pools of hydrates. Meanwhile, the ESAS, still presents large knowledge gaps in many aspects, especially with respect to subsea permafrost distribution and physical properties of bottom sediments. New field data show that the ESAS has an unfrozen (ice-free) upper sediment layer, which in-situ temperature is −1.0 to −1.8 °C and 0.6оС above the freezing point. On one hand, these cold temperature patterns may be related to the presence of subsea permafrost, which currently primarily occurs in the part of the ESAS that is shallower than 100 m, while ice-bearing sediments may also exist locally under deeper water in the Laptev Sea. On the other hand, the negative bottom sediment temperatures of −1.8 °C measured on the Laptev Sea continental slope sediments underlying water columns as deep as down to 330 m may result from dissociation of gas hydrates or possibly from dense water cascading down from the shelf. In contrast, data collected on recent expeditions in the northern Laptev shelf, zones of warmer bottom temperatures are coinciding with methane seeps, likely induced by seismic and tectonic activity in the area. These warm temperatures are not seen in the East Siberian Sea area, not even in areas of methane seeps, yet with little seismic activity.The thermal conductivity and heat capacity of bottom sediments recorded in the database of thermal parameters for the ESAS areas mainly depend on their lithification degree (density or porosity), moisture content, and particle size distribution. The thermal conductivity and heat capacity average about 1.0 W/(m·K) and 2900 kJ/(m3·K), with ±20% and ±10% variance, respectively, in all sampled Arctic sediments to a sub-bottom interval of 0–0.5 m.
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| 1865. |
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| 1866. |
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| 1867. |
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| 1868. |
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| 1869. |
- Clavel, J., et al.
(författare)
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Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. I. An 8 month campaign of monitoring NGC 5548 with IUE
- 1991
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 366:1, s. 64-8181
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Tidskriftsartikel (refereegranskat)abstract
- The authors present emission-line and ultraviolet continuum observations of a type I Seyfert galaxy in which the time resolution is adequate for describing the character of variability. Using the IUE satellite, the nucleus of NGC 5548 was observed every 4 days for a period of 8 months. Its mean properties-continuum shape, line ratios-are not unusual for type I Seyfert galaxies, but it was found to be strongly variable. The ultraviolet continuum flux and broad emission line fluxes varied significantly, going through three large maxima and three deep minima. The great majority of all variations were well resolved in time. The data lend qualitative support to the view that photoionization by the nuclear continuum is responsible for driving the emission lines
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| 1870. |
- Coates, Matthew M., et al.
(författare)
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A comparison of all-cause and cause-specific mortality by household socioeconomic status across seven INDEPTH network health and demographic surveillance systems in sub-Saharan Africa
- 2019
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Ingår i: Global Health Action. - : Taylor & Francis Group. - 1654-9716 .- 1654-9880. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding socioeconomic disparities in all-cause and cause-specific mortality can help inform prevention and treatment strategies.Objectives: To quantify cause-specific mortality rates by socioeconomic status across seven health and demographic surveillance systems (HDSS) in five countries (Ethiopia, Kenya, Malawi, Mozambique, and Nigeria) in the INDEPTH Network in sub-Saharan Africa.Methods: We linked demographic residence data with household survey data containing living standards and education information we used to create a poverty index. Person-years lived and deaths between 2003 and 2016 (periods varied by HDSS) were stratified in each HDSS by age, sex, year, and number of deprivations on the poverty index (0-8). Causes of death were assigned to each death using the InterVA-4 model based on responses to verbal autopsy questionnaires. We estimated rate ratios between socioeconomic groups (2-4 and 5-8 deprivations on our poverty index compared to 0-2 deprivations) for specific causes of death and calculated life expectancy for the deprivation groups.Results: Our pooled data contained almost 3.5 million person-years of observation and 25,038 deaths. All-cause mortality rates were higher among people in households with 5-8 deprivations on our poverty index compared to 0-2 deprivations, controlling for age, sex, and year (rate ratios ranged 1.42 to 2.06 across HDSS sites). The poorest group had consistently higher death rates in communicable, maternal, neonatal, and nutritional conditions (rate ratios ranged 1.34-4.05) and for non-communicable diseases in several sites (1.14-1.93). The disparities in mortality between 5-8 deprivation groups and 0-2 deprivation groups led to lower life expectancy in the higher-deprivation groups by six years in all sites and more than 10 years in five sites.Conclusions: We show large disparities in mortality on the basis of socioeconomic status across seven HDSS in sub-Saharan Africa due to disparities in communicable disease mortality and from non-communicable diseases in some sites. Life expectancy gaps between socioeconomic groups within sites were similar to the gaps between high-income and lower-middle-income countries. Prevention and treatment efforts can benefit from understanding subpopulations facing higher mortality from specific conditions.
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